autophagy, fungi,yeast

[Guest guest]

2009 Aug;7(6):743-52.

Autophagy as an antimicrobial strategy.

Subauste CS.

Case Western Reserve University School of Medicine, 11100 Euclid Avenue,

Cleveland, OH 44106, USA. carlos.subauste@...

Autophagy is a process of lysosomal degradation that was originally described as

a cellular response to adapt to a lack of nutrients and to enable the

elimination of damaged organelles. Autophagy is increasingly recognized as a

process that is also involved in innate and adaptive immune responses against

pathogens. Studies on the regulation of autophagy have uncovered components of

the autophagic cascade that can be manipulated pharmacologically. Approaches to

modulate autophagy may result in novel strategies for the treatment and

prevention of various infections.

PMID: 19681702 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/19681702?ordinalpos=1 & itool=EntrezSystem2.PEn\

trez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA & linkpo\

s=2 & log$=relatedreviews & logdbfrom=pubmed

2009 Jan;16(1):79-86. Epub 2008 Jul 18.

Autophagy in CD4+ T-cell immunity and tolerance.

Lünemann JD, Münz C.

Laboratory of Viral Immunobiology, H. Browne Center for Immunology

and Immune Diseases, The Rockefeller University, Box 390, 1230 York Avenue, New

York, NY 10021-6399, USA.

Autophagy is a homeostatic process that enables eukaryotic cells to deliver

cytoplasmic constituents for lysosomal degradation, to recycle nutrients and to

survive during starvation. In addition to these primordial functions, autophagy

has emerged as a key mechanism in orchestrating innate and adaptive immune

responses to intracellular pathogens. Autophagy restricts viral infections as

well as replication of intracellular bacteria and parasites and delivers

pathogenic determinants for TLR stimulation and for MHC class II presentation to

the adaptive immune system. Apart from its role in defense against pathogens,

autophagy-mediated presentation of self-antigens in the steady state could have

a crucial role in the induction and maintenance of CD4(+) T-cell tolerance. This

review describes the mechanisms by which the immune system utilizes autophagic

degradation of cytoplasmic material to regulate adaptive immune responses.

PMID: 18636073 [PubMed - indexed

2009 Jun 18;5(6):527-49.

Autophagy, immunity, and microbial adaptations.

Deretic V, Levine B.

Department of Molecular Genetics and Microbiology, University of New Mexico

Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.

vderetic@...

Autophagy adjusts cellular biomass and function in response to diverse stimuli,

including infection. Autophagy plays specific roles in shaping immune system

development, fueling host innate and adaptive immune responses, and directly

controlling intracellular microbes as a cell-autonomous innate defense. As an

evolutionary counterpoint, intracellular pathogens have evolved to block

autophagic microbicidal defense and subvert host autophagic responses for their

survival or growth. The ability of eukaryotic pathogens to deploy their own

autophagic machinery may also contribute to microbial pathogenesis. Thus, a

complex interplay between autophagy and microbial adaptations against autophagy

governs the net outcome of host-microbe encounters.

2009 Sep;1793(9):1465-77. Epub 2009 Mar 19.

Autophagy in intracellular bacterial infection.

Campoy E, Colombo MI.

Laboratorio de Biología Celular y Molecular, Instituto de Histología y

Embriología (IHEM)-CONICET, Facultad de Ciencias Médicas, Universidad Nacional

de Cuyo, Casilla de Correo 56, Centro Universitario, Parque General San Martín,

(5500) Mendoza, Argentina.

Numerous pathogens have developed the capacity to invade host cells to be

protected from components of the systemic immune system. However, once in the

host cells they utilize sophisticated strategies to avoid the powerful machinery

built by the cells to kill invading pathogens. In the last few years cumulative

evidence indicates that autophagy is one of the most remarkable tools of the

intracellular host cell defense machinery that bacteria must confront upon cell

invasion. However, several pathogens subvert the autophagic pathway and,

manipulate this process at the molecular level, as a strategy to establish a

persistent infection. In this review we have summarized the interaction between

autophagy and different bacterial pathogens including those that take advantage

of the host cell autophagy, allowing successful colonization, as well as those

microorganisms which are controlled by autophagy as part of the innate

surveillance mechanism.

PMID: 19303905 [PubMed - indexed for MEDLINE]

In silico reconstruction of nutrient-sensing signal transduction pathways in

Aspergillus nidulans

http://www.bioinfo.de/isb/2004040050/

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2009 Oct 6;106(40):17049-54. Epub 2009 Sep 21.

The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein

kinase complex to control autophagy.

Stephan JS, Yeh YY, Ramachandran V, Deminoff SJ, Herman PK.

Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210,

USA.

Macroautophagy (or autophagy) is a conserved degradative pathway that has been

implicated in a number of biological processes, including organismal aging,

innate immunity, and the progression of human cancers. This pathway was

initially identified as a cellular response to nutrient deprivation and is

essential for cell survival during these periods of starvation. Autophagy is

highly regulated and is under the control of a number of signaling pathways,

including the Tor pathway, that coordinate cell growth with nutrient

availability. These pathways appear to target a complex of proteins that

contains the Atg1 protein kinase. The data here show that autophagy in

Saccharomyces cerevisiae is also controlled by the cAMP-dependent protein kinase

(PKA) pathway. Elevated levels of PKA activity inhibited autophagy and

inactivation of the PKA pathway was sufficient to induce a robust autophagy

response. We show that in addition to Atg1, PKA directly phosphorylates Atg13, a

conserved regulator of Atg1 kinase activity. This phosphorylation regulates

Atg13 localization to the preautophagosomal structure, the nucleation site from

which autophagy pathway transport intermediates are formed. Atg13 is also

phosphorylated in a Tor-dependent manner, but these modifications appear to

occur at positions distinct from the PKA phosphorylation sites identified here.

In all, our data indicate that the PKA and Tor pathways function independently

to control autophagy in S. cerevisiae, and that the Atg1/Atg13 kinase complex is

a key site of signal integration within this degradative pathway.

PMID: 19805182 [PubMed - indexed for MEDLINE]

2009 Sep;1793(9):1413-21. Epub 2009 Jan 22.

Regulation of autophagy in yeast Saccharomyces cerevisiae.

Cebollero E, Reggiori F.

Department of Cell Biology and Institute of Biomembranes, University Medical

Centre Utrecht, 3584 CX Utrecht, The Netherlands.

Autophagy is a conserved catabolic process that initially involves the bulk or

the selective engulfment of cytosolic components into double-membrane vesicles

and successively the transport of the sequestered cargo material into the

lysosome/vacuole for degradation. This pathway allows counteracting internal and

external stresses, including changes in the nutrient availability, that alter

the cell metabolic equilibrium. Consequently, the regulation of autophagy is

crucial for maintaining important cellular functions under various conditions

and ultimately it is essential for survival. Yeast Saccharomyces cerevisiae has

been successfully employed as a model system to study autophagy. For instance,

it has allowed the isolation of the factors specifically involved in autophagy,

the Atg proteins, and the characterization of some of their molecular roles. In

addition, this organism also possesses all the principal signaling cascades that

modulate the cell metabolism in response to nutrient availability in higher

eukaryotes, including the TOR and the PKA pathways. Therefore, yeast is an ideal

system to study the regulation of autophagy by these signaling pathways. Here,

we review the current state of our knowledge about the molecular events leading

to the induction or inhibition of autophagy in yeast with special emphasis on

the regulation of the function of Atg proteins.

http://www.ncbi.nlm.nih.gov/pubmed/19344676?ordinalpos=1 & itool=EntrezSystem2.PEn\

trez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA & linkpo\

s=5 & log$=relatedreviews & logdbfrom=pubmed

AUTOPHAGY,PLANTS,MOLDS,

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC527192/

AUTOPHAGY

With these recent discoveries, it is now clear that autophagy can aid in defense

against pathogens, but the microbes can also employ this pathway to promote

their viability

http://media.wiley.com/product_data/excerpt/04/35273145/3527314504.pdf

2009,Autophagy and Its Role in MHC-Mediated Antigen Presentation1

http://www.jimmunol.org/cgi/content/abstract/182/6/3335

2009,HSP90 and HSP90ß Isoforms Selectively Modulate MHC Class II Antigen

Presentation in B Cells1

http://www.jimmunol.org/cgi/content/abstract/182/12/7451

CITED FROM

2000,Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous

Antigen by Major Histocompatibility Complex Class II Proteins

http://jem.rupress.org/cgi/content/abstract/191/9/1513