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Relationships Between Mitochondrial Dynamics and Bioenergetics

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Mitochondrial Dynamics and Neurodegeneration

Abstract

In this chapter we describe the fundamental mechanisms by which mammalian cells regulate energy production, and we put emphasis on the importance of mitochondrial dynamics for the regulation of bioenergetics. We discuss both the impact of shape changes of the mitochondrion on organellar energy production, and the existence of reverse mechanisms of regulation of mitochondrial fusion and fission by the cellular energy state. Hence, in complement to pioneering concepts of metabolic control which only considered the key controlling steps of energy fluxes at the level of the respiratory chain, the recent study of mitochondrial dynamics highlights new possibilities for OXPHOS control. The implications of such a regulatory loop between mitochondrial dynamics and bioenergetics impacts several fields of human biology, as diverse as embryonic development, energy storage, cell motility, lipid and membrane biogenesis, intracellular trafficking and cell death. In addition, most neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Hereditary Spastic Paraplegia are associated with defects in mitochondrial dynamics and bioenergetics. Therefore, to unravel the fundamental mechanisms by which mitochondrial form interacts with mitochondrial function could permit to increase our basic knowledge on the regulation of energy metabolism and to decipher the pathophysiology of a group of rare neuronal diseases.

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Abbreviations

ADP:

adenosine diphosphate

ANT:

adenine nucleotide translocator

ATP:

adenosine triphosphate

CCCP:

carbonyl cyanide m-chlorophenylhydrazone

COX:

cytochrome c oxidase

CM:

cristae membrane

CoQ:

coenzyme Q

Cyt c:

cytochrome c

DAPI:

diamidino-4′,6-phénylindol-2 dichlorhydrate

Δψ:

mitochondrial membrane electric potential

DNP:

2,4-Dinitrophenol

DRP1:

dynamin-related protein 1

EGFP:

enhanced GFP

EM:

electron microscopy

ETC:

electron transfer chain

FADH2:

flavin adenine dinucleotide reduced form

FCCP:

carbonylcyanide-p-trifluoromethoxyphenylhydrazone

FISH:

fluorescent in situ hybridization

FMN:

flavin mononucleotide

4Pi MICROSCOPE:

confocal microscope with two opposing lenses used for high resolution imaging of fluorescence

FRET:

fluorescence resonance energy transfer

GFP:

green fluorescent protein

GTP:

guanidin triphosphate

H2O2 :

hydrogen peroxyde

IBM:

inner boundary membrane

ICS:

intra cristae space

IM:

inner membrane

IMS:

inter-membrane space

JO2 :

respiratory rate

MCA:

metabolic control analysis

mPTP:

mitochondrial permeability transition pore

mt-NETWORK:

mitochondrial network

NADH:

nicotinamide adenine dinucleotide reduced form

OM:

outer membrane

OPA1:

gene encoding a dynamin-related mitochondrial protein causing autosomal dominant optic atrophy

OXPHOS:

oxidative phosphorylation

PDH:

pyruvate dehydrogenase complex

PLD:

phospholipase D

RCR:

respiratory control ratio

RFP:

red fluorescent protein

ROS:

reactive oxygen species

SDH:

succinate dehydrogenase

STED MICROSCOPY:

stimulated emission depletion microscopy

TMRM:

tetramethyl rhodamine methyl ester

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Acknowledgments

We thank the French National Institute for Scientific and Medical Research (INSERM), Université Victor Segalen Bordeaux 2, Région Aquitaine, Ammi, and Cancéropôle Grand Sud-Ouest for financial support. N. Bellance was supported by a Grant from INSERM/Région Aquitaine and G. Benard by a grant from ANR.

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  1. Laboratoire “MRGM” EA4576 (Maladies Rares: Génétique et Métabolisme), Université de Bordeaux, Bordeaux, France

    Giovanni Benard, Nadège Bellance, Caroline Jose & Rodrigue Rossignol

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  1. Giovanni Benard
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  2. Nadège Bellance
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  3. Caroline Jose
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  4. Rodrigue Rossignol
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Correspondence to Rodrigue Rossignol .

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  1. , Department of Pathology, Stanford University School of Medicine, Allardice Way 825, Stanford, 94305, California, USA

    Bingwei Lu

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Benard, G., Bellance, N., Jose, C., Rossignol, R. (2011). Relationships Between Mitochondrial Dynamics and Bioenergetics. In: Lu, B. (eds) Mitochondrial Dynamics and Neurodegeneration. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1291-1_2

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