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Mitochondrial dynamics as regulators of cancer biology

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Abstract

Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease. In cancers, oncogenic signals that drive excessive proliferation, increase intracellular stress, and limit nutrient supply are all able to alter the bioenergetic and biosynthetic requirements of cancer cells. Consequently, mitochondrial function and shape rapidly adapt to these hostile conditions to support cancer cell proliferation and evade activation of cell death programs. In this review, we will discuss the molecular mechanisms governing mitochondrial dynamics and integrate recent insights into how changes in mitochondrial shape affect cellular migration, differentiation, apoptosis, and opportunities for the development of novel targeted cancer therapies.

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Acknowledgements

This work was supported by: NIH Grants CA157740 (J. E. C.) and CA206005 (J. E. C.); the JJR Foundation, the William A. Spivak Fund, the Fridolin Charitable Trust, an American Cancer Society Research Scholar Award, a Leukemia and Lymphoma Society Career Development Award, and an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award. This work was also supported in part by two research Grants (5FY1174 and 1FY13416) from the March of Dimes Foundation, and the Developmental Research Pilot Project Program within the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai.

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  1. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY, 10029, USA

    Andrew Paul Trotta & Jerry Edward Chipuk

  2. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY, 10029, USA

    Andrew Paul Trotta & Jerry Edward Chipuk

  3. The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY, 10029, USA

    Jerry Edward Chipuk

  4. Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY, 10029, USA

    Jerry Edward Chipuk

  5. The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY, 10029, USA

    Jerry Edward Chipuk

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Trotta, A.P., Chipuk, J.E. Mitochondrial dynamics as regulators of cancer biology. Cell. Mol. Life Sci. 74, 1999–2017 (2017). https://doi.org/10.1007/s00018-016-2451-3

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