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Mitochondrial Dynamics and Apoptosis

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Mitochondrial Dynamics and Neurodegeneration

Abstract

The dynamic nature of mitochondria is not only important for maintaining normal healthy cells, but is also very important in the timely execution of apoptosis. The machinery involved in mediating mitochondrial fission and fusion, namely the large GTPases Drp1, OPA1, Mfn1 and Mfn2, can be modulated to either intensify or reduce apoptosis. During the intrinsic/mitochondrial apoptotic pathway, Drp1 promotes mitochondrial fragmentation, while proteolytic cleavage and release of OPA1 from the mitochondria enhances this fragmentation and results in a swollen/altered cristae morphology. Conditions that enhance mitochondrial fusion, such as overexpression of OPA1, Mfn1, Mfn2 or inhibition of Drp1, generally result in a delay of apoptosis while enhancing mitochondrial fission, through overexpression of Drp1 or down regulating OPA1, Mfn1 or Mfn2, augments apoptosis.

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Abbreviations

BH:

Bcl-2 homology

CCCP:

Carbonyl cyanide 3-chlorophenylhydrazone

CMT2A:

Charcot-Marie Tooth Type 2A

GED:

GTPase effector domain

IMM:

Inner mitochondrial membrane

IMS:

Inner membrane space

mdivi-1:

mitochondrial division inhibitor

MEFs:

Mouse embryonic fibroblasts

MOMP:

mitochondrial outer membrane permeabilization

mtPTP:

Mitochondrial permeability transition pore

OMM:

Outer mitochondrial membrane

OMMAD:

Outer mitochondrial membrane associated degradation

SIMH:

Stress induced mitochondrial hyperfusion

TM:

Transmembrane

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Acknowledgements

We would like to thank Dr. Lesley Kane for her thoughtful reading and comments on the chapter and Dr. Jean Claude Martinou for the SIMH image. Work in the Youle Lab is supported in part by the Intramural Research Program, NINDS, NIH.

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  1. Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), 35 Convent Drive, MSC 3704, Building 35/Rm, 2C917, Bethesda, MD, 20892, USA

    Megan M. Cleland & Richard J. Youle

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  1. Megan M. Cleland
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  2. Richard J. Youle
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Correspondence to Richard J. Youle .

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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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© 2011 Springer Science+Business Media B.V.

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Cleland, M.M., Youle, R.J. (2011). Mitochondrial Dynamics and Apoptosis. In: Lu, B. (eds) Mitochondrial Dynamics and Neurodegeneration. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1291-1_4

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