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4.2 Mitochondrial Architecture and Heterogeneity

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Brain mitochondria are heterogeneous in structure, enzyme complement, energy metabolism, motility, and compartmentation. In recent years, the detailed three-dimensional structure of these organelles has been provided by electron tomography, which has generated new paradigms of mitochondrial architecture. Consistent variations are found in mitochondrial structure or enzyme content among various neuronal and neuroglial cell types suggesting differences in functional capacities. Brain energy metabolism depends largely on aerobic glycolysis and displays marked regional differences reflecting differential expression or regulation of mitochondrial enzymes, including within the four major compartments of neurons—axon, dendrite, soma, and synapse. Evidence is building that the functional decline in the aging brain is related to a decrease in mitochondrial viability. On the other side of lifespan, the developing brain uses a proliferation of mitochondria to establish the onset of aerobic metabolism and uses mitochondrial components for programmed cell death crucial for proper development. Mitochondrial heterogeneity has only recently been addressed to understand the dynamics of energy signatures of neuronal cell types, including the actions of signaling molecules targeted to mitochondria. Tools on the horizon should prove useful for probing local control of mitochondrial functioning and the dynamics of signaling, both to and from this organelle.

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Abbreviations

2D:

two dimensional

3D:

three dimensional

ADP:

adenosine diphosphate

ANT:

adenine nucleotide transporter

ATP:

adenosine triphosphate

Bax:

BCL2-associated X protein; Bid, BH3 interacting domain death agonist

CALI:

chromophore-assisted light inactivation

CAT:

computer-aided tomography

DAB:

diaminobenzidine

DCIP:

dichloroindophenol

Drp1:

dynamin-related protein-1

EELS:

electron energy loss spectroscopy

FRET:

fluorescence resonance energy transfer

GABA:

γ-amino butyric acid

GFP:

green fluorescent protein

KAT:

kynurenine aminotransferase

MAC:

mitochondrial-associated adherens complex

MRI:

magnetic resonance imaging

mt:

mitochondrial

NAD:

nicotinamide adenine dinucleotide

NADH:

reduced form of nicotinamide adenine dinucleotide

NADP:

nicotinamide adenine dinucleotide phosphate

NGF:

nerve growth factor

NMDA:

N-methyl d-aspartate

NMR:

nuclear magnetic resonance

OPA1:

optic atrophy 1

PTP:

permeability transition pore

QD:

quantum dot

TCA:

tricarboxylic acid cycle

TIM:

translocase inner membrane

TOM:

translocase outer membrane

VDAC:

voltage-dependent anion channel

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Acknowledgments

Samples for figures were provided by Don Fox, Ella Bossy-Wetzel, and George Spirou. Andrew White and Joshua Brown helped with tomography. Arrowsmith was used for literature searches. This work was supported by NIH grants P41RR04050 and R01 NS14718.

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Perkins, G.A., Ellisman, M. (2007). 4.2 Mitochondrial Architecture and Heterogeneity. In: Lajtha, A., Gibson, G.E., Dienel, G.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30411-3_11

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