(mentions CMT 2A) Multi-site control and regulation of mitochondrial energy prod

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Biochim Biophys Acta. 2010 Mar 9

Multi-site control and regulation of mitochondrial energy production.

Benard G, Bellance N, C, Melser S, Nouette-Gaulain K, Rossignol R.

INSERM, U688, F-33076 Bordeaux cedex, France; Université Victor Segalen-Bordeaux

2, 146 rue Léo-Saignat, 33076 Bordeaux cedex, France.

With the extraordinary progress of mitochondrial science and cell biology, novel

biochemical pathways have emerged as strategic points of bioenergetic regulation

and control. They include mitochondrial fusion, fission and organellar motility

along microtubules and microfilaments (mitochondrial dynamics), mitochondrial

turnover (biogenesis and degradation), and mitochondrial phospholipids

synthesis. Yet, much is still unknown about the mutual interaction between

mitochondrial energy state, biogenesis, dynamics and degradation.

Meanwhile, clinical research into metabolic abnormalities in tumors as diverse

as renal carcinoma, glioblastomas, paragangliomas or skin leiomyomata, has

designated new genes, oncogenes and oncometabolites involved in the regulation

of cellular and mitochondrial energy production.

Furthermore, the examination of rare neurological diseases such as Charcot-Marie

Tooth type 2a, Autosomal Dominant Optic Atrophy, Lethal Defect of Mitochondrial

and Peroxisomal Fission, or Spastic Paraplegia suggested involvement of MFN2,

OPA1/3, DRP1 or Paraplegin, in the auxiliary control of mitochondrial energy

production.

Lastly, advances in the understanding of mitochondrial apoptosis have suggested

a supplementary role for Bcl2 or Bax in the regulation of mitochondrial

respiration and dynamics, which has fostered the investigation of alternative

mechanisms of energy regulation. In this review, we discuss the regulatory

mechanisms of cellular and mitochondrial energy production, and we emphasize the

importance of the study of rare neurological diseases in addition to more common

disorders such as cancer, for the fundamental understanding of cellular and

mitochondrial energy production.