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Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction

Nature Metabolism volume 5, pages 546–562 (2023)Cite this article

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Abstract

Mitochondria have cell-type specific phenotypes, perform dozens of interconnected functions and undergo dynamic and often reversible physiological recalibrations. Given their multifunctional and malleable nature, the frequently used terms ‘mitochondrial function’ and ‘mitochondrial dysfunction’ are misleading misnomers that fail to capture the complexity of mitochondrial biology. To increase the conceptual and experimental specificity in mitochondrial science, we propose a terminology system that distinguishes between (1) cell-dependent properties, (2) molecular features, (3) activities, (4) functions and (5) behaviours. A hierarchical terminology system that accurately captures the multifaceted nature of mitochondria will achieve three important outcomes. It will convey a more holistic picture of mitochondria as we teach the next generations of mitochondrial biologists, maximize progress in the rapidly expanding field of mitochondrial science, and also facilitate synergy with other disciplines. Improving specificity in the language around mitochondrial science is a step towards refining our understanding of the mechanisms by which this unique family of organelles contributes to cellular and organismal health.

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Fig. 1: An integrative approach to mitochondrial biology.
Fig. 2: Different cell types and subcellular compartments contain functionally specialized mitochondrial phenotypes.
Fig. 3: Diversity in mitochondrial morphology.
Fig. 4: Terminology for mitochondrial science organized as a hierarchy of mitochondrial needs.
Fig. 5: Example of measurements across domains of mitochondrial biology.

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Acknowledgements

We are grateful to investigators who have contributed to reveal tissue-type-specific and cell-type-specific mitochondrial phenotypes that served as the foundation and motivation for this Perspective. We apologize to authors whose work could not be included due to space constraints. We thank the Twitter mitochondrial community and C. Schmitt who contributed inputs to Table 1, and to members of the Mitochondrial Psychobiology Laboratory, and the Genoxphos Laboratory for stimulating discussions. Work of J.A.E. is supported by Ministerio de Ciencia, Innovación/Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER; RTI2018-099357-B-I00), the Biomedical Research Networking Center on Frailty and Healthy Ageing (CIBERFES-ISCiii-CB16/10/00289) and the Leducq TNE-17CVD. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work was supported by National Institutes of Health grants R01MH119336, R01MH122706, R01AG066828, R21MH123927 and RF1AG076821, the Wharton Fund and the Baszucki Brain Research Fund (to M.P.).

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Authors and Affiliations

  1. Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Anna S. Monzel & Martin Picard

  2. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain

    José Antonio Enríquez

  3. CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain

    José Antonio Enríquez

  4. Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, NY, USA

    Martin Picard

  5. New York State Psychiatric Institute, New York, NY, USA

    Martin Picard

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M.P. drafted the figures. A.S.M., J.A.E. and M.P. contributed to the literature review and revised the final version of the figures and manuscript.

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Monzel, A.S., Enríquez, J.A. & Picard, M. Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction. Nat Metab 5, 546–562 (2023). https://doi.org/10.1038/s42255-023-00783-1

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