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Mitochondrial heterogeneity and homeostasis through the lens of a neuron

Nature Metabolism volume 4, pages 802–812 (2022)Cite this article

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Abstract

Mitochondria are vital organelles with distinct morphological features and functional properties. The dynamic network of mitochondria undergoes structural and functional adaptations in response to cell-type-specific metabolic demands. Even within the same cell, mitochondria can display wide diversity and separate into functionally distinct subpopulations. Mitochondrial heterogeneity supports unique subcellular functions and is crucial to polarized cells, such as neurons. The spatiotemporal metabolic burden within the complex shape of a neuron requires precisely localized mitochondria. By travelling great lengths throughout neurons and experiencing bouts of immobility, mitochondria meet distant local fuel demands. Understanding mitochondrial heterogeneity and homeostasis mechanisms in neurons provides a framework to probe their significance to many other cell types. Here, we put forth an outline of the multifaceted role of mitochondria in regulating neuronal physiology and cellular functions more broadly.

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Fig. 1: Mitochondrial network in different cell types.
Fig. 2: Mitochondrial morphology and localization in neurons.
Fig. 3: Molecular mechanisms underlying mitochondrial trafficking and positioning.
Fig. 4: Mitochondrial quality-control pathways.

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Acknowledgements

We thank the Pekkurnaz and Wang lab members for discussions. We apologize to colleagues whose work could not be cited owing to space constraints. We thank the following funders: National Institutes of Health (RO1NS089583 and RO1GM143258 to X. W. and R35GM128823 to G. P.), the Parkinson’s Foundation (PF-JFA-1888 to G. P.) and the Chan Zuckerberg Initiative (2020-222005 to G. P.).

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Authors and Affiliations

  1. Neurobiology Department, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA

    Gulcin Pekkurnaz

  2. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA

    Xinnan Wang

  3. Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA

    Xinnan Wang

  4. Maternal & Child Health Research Institute, Stanford University School of Medicine, Stanford, CA, USA

    Xinnan Wang

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  1. Gulcin Pekkurnaz
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Both authors conceived the idea and wrote the paper.

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Correspondence to Gulcin Pekkurnaz or Xinnan Wang.

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X. W. is a co-founder, adviser, and shareholder of AcureX Therapeutics, and a shareholder of Mitokinin Inc. Both companies develop therapeutics that target mitochondria for neurodegenerative diseases. G. P. declares no competing interests.

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Nature Metabolism thanks Evandro Fang and the other, anonymous reviewers for their contribution to the peer review of this work. Primary handling editor: Alfredo Giménez-Cassina, in collaboration with the Nature Metabolism team.

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Pekkurnaz, G., Wang, X. Mitochondrial heterogeneity and homeostasis through the lens of a neuron. Nat Metab 4, 802–812 (2022). https://doi.org/10.1038/s42255-022-00594-w

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