Mitochondria-derived peptides in aging and healthspan
Brendan Miller, … , Kelvin Yen, Pinchas Cohen
Brendan Miller, … , Kelvin Yen, Pinchas Cohen
Published May 2, 2022
Citation Information: J Clin Invest. 2022;132(9):e158449. https://doi.org/10.1172/JCI158449.
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Review Series

Mitochondria-derived peptides in aging and healthspan

Abstract

The mechanisms that explain mitochondrial dysfunction in aging and healthspan continue to be studied, but one element has been unexplored: microproteins. Small open reading frames in circular mitochondria DNA can encode multiple microproteins, called mitochondria-derived peptides (MDPs). Currently, eight MDPs have been published: humanin, MOTS-c, and SHLPs 1–6. This Review describes recent advances in microprotein discovery with a focus on MDPs. It discusses what is currently known about MDPs in aging and how this new understanding could add to the way we understand age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.

Authors

Brendan Miller, Su-Jeong Kim, Hiroshi Kumagai, Kelvin Yen, Pinchas Cohen

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Figure 2

Mitochondria-derived peptides in age-related disease.

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Mitochondria-derived peptides in age-related disease. Three MDPs have be...
Three MDPs have been studied in the context of age-related diseases: humanin, MOTS-c, and SHLP2. Humanin has been shown to mitigate Alzheimer’s disease pathology in rodents, and its levels and genetic variation associate with age and cognition. MOTS-c has been described as an exercise mimetic and prevents muscle atrophy in mice, and its levels and genetic variation associate with age and type 2 diabetes (T2D). SHLP2 functions as a mitochondrial modulator and protein chaperone, and its levels associate with age and prostate cancer.