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  • Review Article
  • Published:

Functions and dysfunctions of mitochondrial dynamics

Nature Reviews Molecular Cell Biology volume 8, pages 870–879 (2007)Cite this article

Key Points

  • Mitochondria are dynamic organelles. They continually fuse and divide, are actively recruited to specific cellular locations and have dynamic structures.

  • Mitochondrial fusion requires three large GTPases: the outer membrane proteins MFN1 and MFN2, and the inner membrane protein OPA1.

  • Mitochondrial fission requires the dynamin GTPase DRP1 and the outer membrane protein FIS1.

  • The fusion and fission of mitochondria have several important functions. These processes control the morphology of mitochondria, allow content exchange between mitochondria, control mitochondrial distribution and facilitate the release of intermembrane space proteins during apoptosis.

  • Several structural changes in mitochondria are important for rapid and efficient apoptosis: the mitochondria must be fragmented, their outer membranes must become permeable and the cristae junctions must be widened.

  • Mitochondrial dynamics is particularly important to neurons, and defects result in neurodegenerative disease.

Abstract

Recent findings have sparked renewed appreciation for the remarkably dynamic nature of mitochondria. These organelles constantly fuse and divide, and are actively transported to specific subcellular locations. These dynamic processes are essential for mammalian development, and defects lead to neurodegenerative disease. But what are the molecular mechanisms that control mitochondrial dynamics, and why are they important for mitochondrial function? We review these issues and explore how defects in mitochondrial dynamics might cause neuronal disease.

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Figure 1: Mitochondria as dynamic organelles.
Figure 2: Mitochondrial fusion and fission regulate morphology.
Figure 3: Mitochondrial fusion.
Figure 4: Mitochondrial fission.
Figure 5: Mitochondrial dynamics protects mitochondrial function.
Figure 6: Mitochondrial dynamics during apoptosis.

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Acknowledgements

This work was supported by grants from the National Institutes of Health. D.C.C. is an Ellison Medical Foundation Senior Scholar in Aging.

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  1. Division of Biology, California Institute of Technology, Pasadena, 91125, California, USA

    Scott A. Detmer & David C. Chan

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  1. Scott A. Detmer
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Glossary

Cristae

Invaginations of the mitochondrial inner membrane.

Nebenkern structure

A cytosolic structure, found in some insect spermatids, that is formed by the fusion of mitochondria.

Anterograde

The direction from the cell body towards the periphery.

Retrograde

The direction from peripheral regions towards the cell body.

Oxidative phosphorylation

A biochemical pathway for ATP production that results in oxygen consumption and is localized to the mitochondrial cristae.

Coiled coil

A structural motif that is formed by polypeptide sequences that contain hydrophobic heptad repeats.

Dynamin

A large GTPase that is thought to mediate vesicle scission during endocytosis.

Mitochondrial membrane potential

The electrochemical gradient that exists across the mitochondrial inner membrane.

Ergosterol

A steroid compound that is a component of yeast cell membranes and which might have a role similar to that of cholesterol in mammalian cell membranes.

SNARE

(soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP) receptor). A highly α-helical protein that mediates the specific fusion of vesicles with target membranes.

F-box protein

A protein containing an F-box motif, a small domain that is used for protein interactions. The best-characterized F-box proteins are components of an E3 ubiquitin ligase, and help in ubiquitin-dependent protein degradation by recognizing specific substrates.

β-barrel protein

A protein composed of a β-sheet that is rolled up into a cylinder. One such mitochondrial β-barrel protein is VDAC (voltage-dependent anion channel), which forms a pore in the outer membrane.

Kinesin

A microtubule-based molecular motor protein that is most often directed towards the plus end of microtubules.

Dynein

A microtubule-based molecular motor that is directed towards the minus end of microtubules.

EF-hand domain

A helix-loop-helix protein motif that can bind a Ca2+ ion.

Mitochondrial F1F0 ATP synthase

A large, multisubunit enzyme embedded in the mitochondrial cristae that uses the proton gradient across the inner membrane to synthesize ATP.

Mitochondrial DNA

(mtDNA). A circular genome (∼16 kb in mammals) located in the mitochondrial matrix that encodes 13 polypeptides of the electron transport chain, 22 tRNAs and 2 rRNAs.

Nucleoid

A compacted mass of DNA. Mitochondrial DNA is organized into nucleoids, each consisting of several mitochondrial genomes.

Chemotaxis

The directed movement of cells in response to a chemical stimulus.

Mitochondrial outer membrane permeabilization

(MOMP). The opening of pores in the mitochondrial outer membrane — an early event during apoptosis that releases apoptotic factors from the mitochondrial intermembrane space.

Haploinsufficiency

A genetic state in diploids in which a single functional copy of a gene is insufficient to maintain a normal phenotype.

Sural nerve

A sensory nerve innervating the calf and foot that is commonly investigated by biopsy for the evaluation of peripheral neuropathies.

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Detmer, S., Chan, D. Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8, 870–879 (2007). https://doi.org/10.1038/nrm2275

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