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Mitochondrial Dynamics and Autophagy

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Mitochondrial Dynamics and Neurodegeneration

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Abstract

Efficient mitochondrial quality control is critical for maintenance of a healthy mitochondrial population. Both mitochondrial dynamics and selective mitochondrial autophagy, termed mitophagy, contribute to mitochondrial turnover and quality control. Mitochondrial fusion and fission allow for complementation of mitochondrial solutes, proteins, and DNA but also for generation of unequal daughter organelles. Selective fusion is utilized for incorporation of polarized mitochondria back into the network, while a depolarized mitochondrion will not fuse, but instead will be targeted for elimination by mitophagy. Mitophagy is dependent on mitochondrial dysfunction, such as depolarization, and a number of proteins are required for core autophagic machinery, signaling, and mitochondrial segregation and targeting. The relationship between mitochondrial dynamics and autophagy and how they may contribute to both mitochondrial and cellular quality control is beginning to be elucidated. Even with the questions that remain in regards to the regulation and interdependence of mitochondrial dynamics and mitophagy, it is clear that alterations in these processes lead to mitochondrial dysfunction and pathological states such as neurodegeneration.

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Abbreviations

A9-DA:

A9-subtype dopaminergic neurons of the substantia nigra parscompacta

AD:

Alzheimer’s disease

ALS:

amyotrophic lateral sclerosis

AMPK:

5′adenosine-monophosphate activated protein kinase

ATG:

autophagy-related genes

CA:

constitutively active

CCCP:

carbonyl cyanide m-chlorophenylhydrazone

CMA:

chaperone-mediated autophagy

CMT2A:

Charcot-Marie-Tooth neuropathy type 2A

Cvt:

cytoplasmic to vacuole targeting

DA:

dopaminergic

DLB:

dementia with Lewy Bodies

DN:

dominant negative

DNM1L:

dynamin 1-like

Drp1:

dynamin related protein 1

ER:

endoplasmic reticulum

ERK1/2:

extracellular signal-regulated protein kinase 1/2

ETC:

electron transport chain

Fzo1p:

fuzzy onion protein

GAP:

GTPase-activating protein

HIF:

hypoxia-inducing factor

LAMP-2A:

lysosomal-associated membrane protein 2A

LC3; (MAP)LC3:

microtubule-associated protein light chain 3

MAO:

monoamine oxidase

mdivi-1:

mitochondrial division inhibitor

Mfn1/2:

mitofusin 1 and 2

mPTP:

mitochondrial permeability transition pore

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mtDNA:

mitochondrial DNA

mTOR:

mammalian target of Rapamycin

mtPA-GFP:

mitochondrial photoactivatable green fluorescent protein

NGF:

nerve growth factor

OPA1:

optic atrophy protein 1

PBMC:

peripheral blood mononuclear cells

PD:

Parkinson’s disease

PE:

phosphatidylethanolamine

PI:

phosphatidylinositol

PINK1:

PTEN-induced kinase 1

RGC:

retinal ganglion cells

Rheb:

Ras homolog enriched in brain

ROS:

reactive oxygen species

TMRE:

tetramethylrhodamine ethyl ester

TOR:

target of Rapamycin

TORC1/2:

TOR complex 1 and 2

Ulk1/2:

Unc-51-like kinase 1 and 2

VDAC1:

voltage-dependent anion channel 1

Vps:

vacuolar protein-sorting.

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Acknowledgements

We are grateful to Drs. Marc Liesa, Gilad Twig, and Dani Dagan for insightful comments during the writing of this chapter.

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Authors and Affiliations

  1. Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, Boston, MA, USA

    Linsey Stiles & Orian Shirihai

  2. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA

    Linsey Stiles

  3. Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA

    Andrew Ferree

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  1. Linsey Stiles
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Correspondence to Orian Shirihai .

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    Bingwei Lu

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Stiles, L., Ferree, A., Shirihai, O. (2011). Mitochondrial Dynamics and Autophagy. In: Lu, B. (eds) Mitochondrial Dynamics and Neurodegeneration. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1291-1_3

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