Re: Re: Melatonin-mitochondria Interplay in Health and Disease.

[Guest guest]

Thank you very much, Nikki, I  really appreciate it.  

 

Darla,

pdf of the second one here:

http://www.bioscience.org/u37153137/gaDTRQo7632rgysaGWQYT64356/2007/v12/af/2116/2116.pdf

>

> I am trying to puzzle together some of the mystery that is my son's

> dependence on melatonin - which has always worried me - he simply is unable

> to function without it. And I don't mean just sleep, I mean that he is

> dependent on it for a vastly improved quality of life. This is deeply

> puzzling to me as I have yet to encounter any other ASD child with a

> similar response. He presents with some symptoms that a paed neurologist

> speculated could be metabolic or mitochondrial in orgin (a neuromuscular

> issue) and I wonder if there is some correlation between the oxidative

> stress / nitrosative stress aspects of melatonin and his possible meta/mito

> issues. I would really like to read these full articles - is there anyone

> who might have access who would kindly be able to access it for me? Or

> does anyone know how I might pay to access them? (these are pubmed searches)

> Melatonin-mitochondria Interplay in Health and Disease.

>

> Castroviejo DA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuthor%5D>

> , López LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAuthor%5D>

> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> , López A<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%5D>

> , García JA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuthor%5D>

> , Reiter RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D>

> .

>

> Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la

> Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.

> dacuna@<http://health.groups.yahoo.com/group/Meta-mito-autism/post?postID=MC_sFtBBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ>

> .

> Abstract

>

> Although two main hypotheses of mitochondrial origin have been proposed,

> i.e., the autogenous and the endosymbiotic, only the second is being

> seriously considered currently. The 'hydrogen hypothesis' invokes metabolic

> symbiosis as the driving force for a symbiotic association between an

> anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the

> symbiont) that was able to respire, but which generated molecular hydrogen

> as an end product of anaerobic metabolism. The resulting proto-eukaryotic

> cell would have acquired the essentials of eukaryotic energy metabolism,

> evolving not only aerobic respiration, but also the physiological cost of

> the oxygen consumption, i.e., generation of reactive oxygen species (ROS)

> and the associated oxidative damage. This is not the only price to pay for

> respiring oxygen: mitochondria possess nitric oxide (NO·) for regulatory

> purposes but, in some instances it may react with superoxide anion radical

> to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite

> anion, and the subsequent nitrosative damage. New mitochondria contain

> their own genome with a modified genetic code that is highly conserved

> among mammals. The transcription of certain mitochondrial genes may depend

> on the redox potential of the mitochondrial membrane. Mitochondria are

> related to the life and death of cells. They are involved in energy

> production and conservation, having an uncoupling mechanism to produce heat

> instead of ATP, but they are also involved in programmed cell death.

> Increasing evidence suggest the participation of mitochondria in

> neurodegenerative and neuromuscular diseases involving alterations in both

> nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful

> antioxidant and anti-inflammatory and increasing experimental and clinical

> evidence shows its beneficial effects against oxidative/nitrosative stress

> status, including that involving mitochondrial dysfunction. This review

> summarizes the data and mechanisms of action of melatonin in relation to

> mitochondrial pathologies.

>

> *Melatonin role in the mitochondrial function.*

> Acuna-Castroviejo

> D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5BAuthor%5D>

> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> , MI<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor%5D>

> , LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>

> .

> S

>

> Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de

> Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@...

> Abstract

>

> Melatonin is an ancient molecule

> present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in

> unicellular organisms at the very early moment of life. Initially

> identified as a secretory product of the pineal gland in mammals and in

> other species, it was considered a hormone related to reproduction. The

> evidence that melatonin is produced in many organs and tissues of the body,

> reaching concentrations higher than in the blood, support the multiplicity

> of the melatonin actions. The best-known actions of melatonin, currently

> supported by experimental and clinical data, include antioxidant and

> anti-inflammatory abilities, some of them involving genomic regulation of a

> series of enzymes. Besides, melatonin displays anticonvulsant and

> antiexcitotoxic properties. Most of the beneficial consequences resulting

> from melatonin administration may depend on its effects on mitochondrial

> physiology. The physiological effects of melatonin on normal mitochondria,

> its role to prevent mitochondrial impairment, energy failure, and apoptosis

> in oxidatively-damaged mitochondria, and the beneficial effects of the

> administration of melatonin in experimental and clinical diseases involving

> mitochondrial dysfunction and cell death, are revised.

>

[Guest guest]

Natasa, thanks for those links, they were very interesting.  I haven't taken him off of the melatonin in years but I seem to recall that the last time I accidentally ran out of it the effect was pretty immediate although it did get worse as the days passed.  I think his sleep immediately decreased by about 2 - 3 hours per night.  Remembering this makes me think that maybe your speculation about it " just " being about the sleep is probably right and maybe I am complicating this more than I need to.  It just makes me somewhat anxious that he is so reliant on this supplement for so long and doesn't seem to be moving past his dependency on it.  It's been 6 years now that he's been on it with no breaks.  Maybe I shouldn't be concerned about it?  Anyone? 

A while back I thought that his development was slowing down or just not going as fast as it had been previously and so I increased the dose and BAM there he went, back to ticking along nicely and making good progress, the effect was noticeable within about a week.  I hadn't increased the dose in a few years though and he's obviously grown much much bigger.  

As far as anti-inflammatory - we used to see some little bursts of difference when he had Neurofen (this was when he was younger) but here in the last few years, giving him neurofen does not make any difference to him either way. However I recognise that the anti-inflammatory action could be different between the 2. 

Weirdly he used to display terrible behaviour during sleep - I used to think that he was having seizures during his sleep, he had lots of jerking movements and soaking the bed with sweats.  The jerking and bed sweats decreased with Epsom salts and I assume that the melatonin also helped with this.  However,  I think some of it might have been from his hypervigilliant anxious " strung-out " disposition - just too much adrenaline being dumped into his little body. 

Thanks so much for the links and info.

 

These are very interesting Darla (unfortunately not available through my uni subscription).  Melatonin also has relatively strong antiinflammatory effects, so could be that...  If you stop supplementing it how soon do you see deterioration of symptoms - is it almost immediate or takes weeks or months to notice?

Another possibility is that melatonin affects his quality of sleep in such a way that it affects everything else - I believe 'dysfunctional' sleep (with unregulated cycles etc, so called circadian disorder) can have deep effects on neurotransmitters and hormones during waking hours.

BTW Have you seen this http://www.medpagetoday.com/PrimaryCare/SleepDisorders/3574

Now digressing but we saw this REM behaviour disorder (sitting up, punching and pulling hair in sleep) when first starting LDN years ago. Many report the same thing... No idea what it means and whether linked to melatonin etc but very intriguing.  http://en.wikipedia.org/wiki/Rapid_eye_movement_behavior_disorderv

 

 

 

 

>> I am trying to puzzle together some of the mystery that is my son's

> dependence on melatonin - which has always worried me - he simply is unable> to function without it. And I don't mean just sleep, I mean that he is> dependent on it for a vastly improved quality of life. This is deeply

> puzzling to me as I have yet to encounter any other ASD child with a> similar response. He presents with some symptoms that a paed neurologist> speculated could be metabolic or mitochondrial in orgin (a neuromuscular

> issue) and I wonder if there is some correlation between the oxidative> stress / nitrosative stress aspects of melatonin and his possible meta/mito> issues. I would really like to read these full articles - is there anyone

> who might have access who would kindly be able to access it for me? Or> does anyone know how I might pay to access them? (these are pubmed searches)> Melatonin-mitochondria Interplay in Health and Disease.

> > Castroviejo DA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuthor%5D>

> , López LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAuthor%5D>> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> , López A<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%5D>> , García JA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuthor%5D>

> , Reiter RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D>> .>

> Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la> Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.> dacuna@<http://health.groups.yahoo.com/group/Meta-mito-autism/post?postID=MC_sFtBBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ>

> .> Abstract> > Although two main hypotheses of mitochondrial origin have been proposed,> i.e., the autogenous and the endosymbiotic, only the second is being> seriously considered currently. The 'hydrogen hypothesis' invokes metabolic

> symbiosis as the driving force for a symbiotic association between an> anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the> symbiont) that was able to respire, but which generated molecular hydrogen

> as an end product of anaerobic metabolism. The resulting proto-eukaryotic> cell would have acquired the essentials of eukaryotic energy metabolism,> evolving not only aerobic respiration, but also the physiological cost of

> the oxygen consumption, i.e., generation of reactive oxygen species (ROS)> and the associated oxidative damage. This is not the only price to pay for> respiring oxygen: mitochondria possess nitric oxide (NO·) for regulatory

> purposes but, in some instances it may react with superoxide anion radical> to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite> anion, and the subsequent nitrosative damage. New mitochondria contain

> their own genome with a modified genetic code that is highly conserved> among mammals. The transcription of certain mitochondrial genes may depend> on the redox potential of the mitochondrial membrane. Mitochondria are

> related to the life and death of cells. They are involved in energy> production and conservation, having an uncoupling mechanism to produce heat> instead of ATP, but they are also involved in programmed cell death.

> Increasing evidence suggest the participation of mitochondria in> neurodegenerative and neuromuscular diseases involving alterations in both> nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful

> antioxidant and anti-inflammatory and increasing experimental and clinical> evidence shows its beneficial effects against oxidative/nitrosative stress> status, including that involving mitochondrial dysfunction. This review

> summarizes the data and mechanisms of action of melatonin in relation to> mitochondrial pathologies.> > *Melatonin role in the mitochondrial function.*> Acuna-Castroviejo

> D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5BAuthor%5D>> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> , MI<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor%5D>> , LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>

> .> S> > Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de> Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@...

> Abstract> > Melatonin is an ancient molecule> present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in

> unicellular organisms at the very early moment of life. Initially> identified as a secretory product of the pineal gland in mammals and in> other species, it was considered a hormone related to reproduction. The

> evidence that melatonin is produced in many organs and tissues of the body,> reaching concentrations higher than in the blood, support the multiplicity> of the melatonin actions. The best-known actions of melatonin, currently

> supported by experimental and clinical data, include antioxidant and> anti-inflammatory abilities, some of them involving genomic regulation of a> series of enzymes. Besides, melatonin displays anticonvulsant and

> antiexcitotoxic properties. Most of the beneficial consequences resulting> from melatonin administration may depend on its effects on mitochondrial> physiology. The physiological effects of melatonin on normal mitochondria,

> its role to prevent mitochondrial impairment, energy failure, and apoptosis> in oxidatively-damaged mitochondria, and the beneficial effects of the> administration of melatonin in experimental and clinical diseases involving

> mitochondrial dysfunction and cell death, are revised.>

[Guest guest]

Dear Darla,

Melatonin has no significant side effects but I fully understand your concerns about long term dependence. Have you tried decreasing melatonin dose VERY slowly, i.e 1mg over two weeks, and see if you can stop it if no problems?

This is what I would try but I am just a NHS doctor, not specialised in alternative medicine.

Best

Mirela

These are very interesting Darla (unfortunately not available through my uni subscription). Melatonin also has relatively strong antiinflammatory effects, so could be that... If you stop supplementing it how soon do you see deterioration of symptoms - is it almost immediate or takes weeks or months to notice?

Another possibility is that melatonin affects his quality of sleep in such a way that it affects everything else - I believe 'dysfunctional' sleep (with unregulated cycles etc, so called circadian disorder) can have deep effects on neurotransmitters and hormones during waking hours.

BTW Have you seen this http://www.medpagetoday.com/PrimaryCare/SleepDisorders/3574

Now digressing but we saw this REM behaviour disorder (sitting up, punching and pulling hair in sleep) when first starting LDN years ago. Many report the same thing... No idea what it means and whether linked to melatonin etc but very intriguing. http://en.wikipedia.org/wiki/Rapid_eye_movement_behavior_disorderv

>

> I am trying to puzzle together some of the mystery that is my son's> dependence on melatonin - which has always worried me - he simply is unable> to function without it. And I don't mean just sleep, I mean that he is> dependent on it for a vastly improved quality of life. This is deeply> puzzling to me as I have yet to encounter any other ASD child with a> similar response. He presents with some symptoms that a paed neurologist> speculated could be metabolic or mitochondrial in orgin (a neuromuscular> issue) and I wonder if there is some correlation between the oxidative> stress / nitrosative stress aspects of melatonin and his possible meta/mito> issues. I would really like to read these full articles - is there anyone> who might have access who would kindly be able to access it for me? Or> does anyone know how I might pay to access them? (these

are pubmed searches)> Melatonin-mitochondria Interplay in Health and Disease.>

> Castroviejo DA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuthor%5D>> , López LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAuthor%5D>> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>> , López A<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%5D>> , García JA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuthor%5D>> , Reiter RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D>> .>

> Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la> Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.> dacuna@<http://health.groups.yahoo.com/group/Meta-mito-autism/post?postID=MC_sFtBBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ>

> .> Abstract> > Although two main hypotheses of mitochondrial origin have been proposed,> i.e., the autogenous and the endosymbiotic, only the second is being> seriously considered currently. The 'hydrogen hypothesis' invokes metabolic> symbiosis as the driving force for a symbiotic association between an> anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the> symbiont) that was able to respire, but which generated molecular hydrogen> as an end product of anaerobic metabolism. The resulting proto-eukaryotic> cell would have acquired the essentials of eukaryotic energy metabolism,> evolving not only aerobic respiration, but also the physiological cost of> the oxygen consumption, i.e., generation of reactive oxygen species (ROS)> and the associated oxidative damage. This is not the only price to pay for>

respiring oxygen: mitochondria possess nitric oxide (NO·) for regulatory> purposes but, in some instances it may react with superoxide anion radical> to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite> anion, and the subsequent nitrosative damage. New mitochondria contain> their own genome with a modified genetic code that is highly conserved> among mammals. The transcription of certain mitochondrial genes may depend> on the redox potential of the mitochondrial membrane. Mitochondria are> related to the life and death of cells. They are involved in energy> production and conservation, having an uncoupling mechanism to produce heat> instead of ATP, but they are also involved in programmed cell death.> Increasing evidence suggest the participation of mitochondria in> neurodegenerative and neuromuscular diseases involving alterations in both>

nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful> antioxidant and anti-inflammatory and increasing experimental and clinical> evidence shows its beneficial effects against oxidative/nitrosative stress> status, including that involving mitochondrial dysfunction. This review> summarizes the data and mechanisms of action of melatonin in relation to> mitochondrial pathologies.>

> *Melatonin role in the mitochondrial function.*> Acuna-Castroviejo> D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5BAuthor%5D>> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>> , MI<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor%5D>> , LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>>

..

> S> > Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de> Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@...

> Abstract> > Melatonin is an ancient molecule> present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in

> unicellular organisms at the very early moment of life. Initially> identified as a secretory product of the pineal gland in mammals and in> other species, it was considered a hormone related to reproduction. The> evidence that melatonin is produced in many organs and tissues of the body,> reaching concentrations higher than in the blood, support the multiplicity> of the melatonin actions. The best-known actions of melatonin, currently> supported by experimental and clinical data, include antioxidant and> anti-inflammatory abilities, some of them involving genomic regulation of a> series of enzymes. Besides, melatonin displays anticonvulsant and> antiexcitotoxic properties. Most of the beneficial consequences resulting> from melatonin administration may depend on its effects on mitochondrial> physiology. The physiological effects of melatonin on

normal mitochondria,> its role to prevent mitochondrial impairment, energy failure, and apoptosis> in oxidatively-damaged mitochondria, and the beneficial effects of the> administration of melatonin in experimental and clinical diseases involving> mitochondrial dysfunction and cell death, are revised.>

[Guest guest]

Thanks for the comments, Natasa - I have been following the 5htp threads with interest - can you tell me, does the 5htp have any taste or odor, would it be dissolvable in youghurt and not detectable - there could be no " grains " or lumps of it or won't take it.

Re the melatonin has always been on Kirkman's melatonin, I've never tried any other kind. As far as I know, it is still on prescription only here in the UK.  's GP said he could not prescribe it except for elderly folks but I wasn't keen to switch brands anyway. We started with the Kirkman's melatonin plus which has magnesium.   then refused to take the yoghurts a while back so I had to switch him to the Kirkman's chewables.  I think that the chewables are not quite as efficacious for him as the capsules, it is possible that he does not chew them adequately though and that this affects their absorption but hey, I have no choice, he flat out refuses to take them in the youghurt anymore.

I buy the Kirkman's in bulk in the US and either have someone ship it here or collect it when I go there. Dx

 

Yes that neg effect being so immediate does hint at some action of

melatonin that is more direct than 'just' mito protection. We have had

great improvements in sleep quality after starting 5-htp - not much

change in length of sleep (ds has always been an over-sleeper, needing

11-12 hours min, and that never being enough...), but just waking up

much more refreshed, less foggy and irritable/anxious etc. Maybe

something to consider as a replacement or addition to melatonin? btw do

you need a prescription for it or get it from abroad? Is there a way of

getting it here now without rx?

Natasa

> > >

> > > I am trying to puzzle together some of the mystery that is my

son's

> > > dependence on melatonin - which has always worried me - he simply

is

> > unable

> > > to function without it. And I don't mean just sleep, I mean that

he is

> > > dependent on it for a vastly improved quality of life. This is

deeply

> > > puzzling to me as I have yet to encounter any other ASD child with

a

> > > similar response. He presents with some symptoms that a paed

neurologist

> > > speculated could be metabolic or mitochondrial in orgin (a

neuromuscular

> > > issue) and I wonder if there is some correlation between the

oxidative

> > > stress / nitrosative stress aspects of melatonin and his possible

> > meta/mito

> > > issues. I would really like to read these full articles - is there

anyone

> > > who might have access who would kindly be able to access it for

me? Or

> > > does anyone know how I might pay to access them? (these are pubmed

> > searches)

> > > Melatonin-mitochondria Interplay in Health and Disease.

> > >

> > > Castroviejo DA<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuthor%\

5D

> > >

> > > , López LC<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAuthor%5\

D>

> > > , Escames G<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> > > , López A<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%5D\

>

> > > , García JA<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuthor%\

5D

> > >

> > > , Reiter RJ<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D>

> > > .

> > >

> > > Centro de Investigación Biomédica, Parque Tecnológico

de Ciencias de

> > la

> > > Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada,

Spain.

> > > dacuna@<

> >

http://health.groups.yahoo.com/group/Meta-mito-autism/post?postID=MC_sFt\

BBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ

> > >

> >

> > > .

> > > Abstract

> > >

> > > Although two main hypotheses of mitochondrial origin have been

proposed,

> > > i.e., the autogenous and the endosymbiotic, only the second is

being

> > > seriously considered currently. The 'hydrogen hypothesis' invokes

> > metabolic

> > > symbiosis as the driving force for a symbiotic association between

an

> > > anaerobic, strictly hydrogen-dependent (the host) and an

eubacterium (the

> > > symbiont) that was able to respire, but which generated molecular

> > hydrogen

> > > as an end product of anaerobic metabolism. The resulting

proto-eukaryotic

> > > cell would have acquired the essentials of eukaryotic energy

metabolism,

> > > evolving not only aerobic respiration, but also the physiological

cost of

> > > the oxygen consumption, i.e., generation of reactive oxygen

species (ROS)

> > > and the associated oxidative damage. This is not the only price to

pay

> > for

> > > respiring oxygen: mitochondria possess nitric oxide (NO·) for

regulatory

> > > purposes but, in some instances it may react with superoxide anion

> > radical

> > > to produce the toxic reactive nitrogen species (RNS), i.e.

peroxynitrite

> > > anion, and the subsequent nitrosative damage. New mitochondria

contain

> > > their own genome with a modified genetic code that is highly

conserved

> > > among mammals. The transcription of certain mitochondrial genes

may

> > depend

> > > on the redox potential of the mitochondrial membrane. Mitochondria

are

> > > related to the life and death of cells. They are involved in

energy

> > > production and conservation, having an uncoupling mechanism to

produce

> > heat

> > > instead of ATP, but they are also involved in programmed cell

death.

> > > Increasing evidence suggest the participation of mitochondria in

> > > neurodegenerative and neuromuscular diseases involving alterations

in

> > both

> > > nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known

> > powerful

> > > antioxidant and anti-inflammatory and increasing experimental and

> > clinical

> > > evidence shows its beneficial effects against

oxidative/nitrosative

> > stress

> > > status, including that involving mitochondrial dysfunction. This

review

> > > summarizes the data and mechanisms of action of melatonin in

relation to

> > > mitochondrial pathologies.

> > >

> > > *Melatonin role in the mitochondrial function.*

> > > Acuna-Castroviejo

> > > D<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5BAu\

thor%5D

> > >

> > > , Escames G<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> > > , MI<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor%5D\

>

> > > , LC<

> >

http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>

> > > .

> > > S

> > >

> > > Departamento de Fisiologia, Instituto de Biotecnologia,

Universidad de

> > > Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@

> >

> > > Abstract

> > >

> > > Melatonin is an ancient molecule

> > > present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in

> >

> > > unicellular organisms at the very early moment of life. Initially

> > > identified as a secretory product of the pineal gland in mammals

and in

> > > other species, it was considered a hormone related to

reproduction. The

> > > evidence that melatonin is produced in many organs and tissues of

the

> > body,

> > > reaching concentrations higher than in the blood, support the

> > multiplicity

> > > of the melatonin actions. The best-known actions of melatonin,

currently

> > > supported by experimental and clinical data, include antioxidant

and

> > > anti-inflammatory abilities, some of them involving genomic

regulation

> > of a

> > > series of enzymes. Besides, melatonin displays anticonvulsant and

> > > antiexcitotoxic properties. Most of the beneficial consequences

resulting

> > > from melatonin administration may depend on its effects on

mitochondrial

> > > physiology. The physiological effects of melatonin on normal

> > mitochondria,

> > > its role to prevent mitochondrial impairment, energy failure, and

> > apoptosis

> > > in oxidatively-damaged mitochondria, and the beneficial effects of

the

> > > administration of melatonin in experimental and clinical diseases

> > involving

> > > mitochondrial dysfunction and cell death, are revised.

> > >

> >

> >

> >

>