From Mitochondria to Cells to Humans: Targeting Bioenergetics in Aging and Disease

Elsevier

Available online 17 February 2023, 106391

The International Journal of Biochemistry & Cell BiologyAuthor links open overlay panel, , ABSTRACT

In vivo control over metabolism is at the cutting edge of biomedical research. The particulars of mitochondrial function are especially important to understand in vivo to progress metabolic therapies that will be relevant for diseases of aging. Understanding the differences between how mitochondria function in vitro versus in vivo will be a necessary challenge to overcome to achieve mitochondrial medicine. In this article we outline how discoveries in invertebrate models will be informative for understanding the basic biology of mitochondria to streamline translation to mammals and eventually to humans. Further, we highlight examples of how what is known about mitochondria in vitro is translatable to in vivo models and, in some cases, to human diseases.

Section snippetsINTRODUCTION

Mitochondria are evolutionarily ancient organelles that transform the chemical energy taken in from the environment (i.e. food) into usable energy for cells to function and thrive. This energy conversion happens through a potential energy intermediate that consists of a proton electrochemical gradient across the inner mitochondrial membrane called protonmotive force (PMF). PMF is created via oxidation of metabolites in the mitochondrial electron transport system (ETS), where redox reactions and

Conclusion

Overall, we propose that the basic principles of bioenergetics first described in isolated mitochondria can be applied to in vivo models and can be explored further in the realm of basic biology using invertebrates (Fig. 1). These models can harness the power of cutting-edge technologies to inform mammalian in situ experiments to bridge the gap between isolated bioenergetics and human mitochondrial health. This gap must be bridged at the level of basic biology to effectively move laboratory

Author’s Contributions

BJB wrote and revised the manuscript, GP wrote and revised the manuscript, DJM provided critical feedback and revised the manuscript.

Conflicts of Interest

The authors declare there are no conflicts of interest to disclose.

ACKNOWLEDGEMENTS

BJB and GP are supported by the Biological Mechanisms for Healthy Aging (BMHA) Training Grant NIH T32AG066574. Research and ideas contributing to this review were supported by P01 AG001751.

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