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Post-translational modifications in mitochondria: protein signaling in the powerhouse

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Abstract

There is an intimate interplay between cellular metabolism and the pathophysiology of disease. Mitochondria are essential to maintaining and regulating metabolic function of cells and organs. Mitochondrial dysfunction is implicated in diverse diseases, such as cardiovascular disease, diabetes and metabolic syndrome, neurodegeneration, cancer, and aging. Multiple reversible post-translational protein modifications are located in the mitochondria that are responsive to nutrient availability and redox conditions, and which can act in protein–protein interactions to modify diverse mitochondrial functions. Included in this are physiologic redox signaling via reactive oxygen and nitrogen species, phosphorylation, O-GlcNAcylation, acetylation, and succinylation, among others. With the advent of mass proteomic screening techniques, there has been a vast increase in the array of known mitochondrial post-translational modifications and their protein targets. The functional significance of these processes in disease etiology, and the pathologic response to their disruption, are still under investigation. However, many of these reversible modifications act as regulatory mechanisms in mitochondria and show promise for mitochondrial-targeted therapeutic strategies. This review addresses the current knowledge of post-translational processing and signaling mechanisms in mitochondria, and their implications in health and disease.

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Acknowledgments

This project was supported by grants from the National Institutes of Health (NHLBI) 1F31HL126489-01A1 to ARS, and the Muscular Dystrophy Association (MDA) and the Friedreich’s Ataxia Research Alliance (FARA) to RMP.

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Authors and Affiliations

  1. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Amanda R. Stram

  2. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    R. Mark Payne

  3. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA

    Amanda R. Stram & R. Mark Payne

  4. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St., Room R4-302b, Indianapolis, IN, 46202, USA

    Amanda R. Stram & R. Mark Payne

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  1. Amanda R. Stram
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Correspondence to R. Mark Payne.

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Stram, A.R., Payne, R.M. Post-translational modifications in mitochondria: protein signaling in the powerhouse. Cell. Mol. Life Sci. 73, 4063–4073 (2016). https://doi.org/10.1007/s00018-016-2280-4

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  • DOI: https://doi.org/10.1007/s00018-016-2280-4

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