Mitochondrial-derived peptides: New markers for cardiometabolic dysfunction.

Archives of cardiovascular diseases2022PMID: 34972639

View on PubMed DOI: 10.1016/j.acvd.2021.10.013

Plain Language Summary

Review examining mitochondria-derived peptides—humanin, MOTS-c, and SHLPs—as circulating biomarkers of cardiometabolic dysfunction, covering how mitochondrial stress alters MDP production, their tissue distribution and secretion patterns, and their potential as blood-based diagnostic and prognostic markers for cardiovascular and metabolic disease. Positions MDPs as a novel biomarker class for cardiometabolic medicine. Establishes the conceptual basis for MOTS-c as a cardiometabolic biomarker—arguing that because MDPs reflect real-time mitochondrial functional status, they can provide diagnostic information about the mitochondrial dysfunction that underlies cardiovascular and metabolic disease progression before irreversible organ damage occurs.

Abstract

Great attention is being paid to the evaluation of new markers in blood circulation for the estimation of tissue metabolism disturbance. This endogenous disturbance may contribute to the onset and progression of cardiometabolic disease. In addition to their role in energy production and metabolism, mitochondria play a main function in cellular mechanisms, including apoptosis, oxidative stress and calcium homeostasis. Mitochondria produce mitochondrial-derived peptides that mediate the transcriptional stress response by translocating into the nucleus and interacting with deoxyribonucleic acid. This class of peptides includes humanin, mitochondrial open reading frame of the 12S ribosomal ribonucleic acid type c (MOTS-c) and small humanin-like peptides. Mitochondrial-derived peptides are regulators of metabolism, exerting cytoprotective effects through antioxidative stress, anti-inflammatory responses and antiapoptosis; they are emerging biomarkers reflecting mitochondrial function, and the circulating concentration of these proteins can be used to diagnose cardiometabolic dysfunction. The aims of this review are: (1) to describe the emerging role for mitochondrial-derived peptides as biomarkers; and (2) to discuss the therapeutic application of these peptides.

Authors

Rochette, Luc; Rigal, Eve; Dogon, Geoffrey; Malka, Gabriel; Zeller, Marianne; Vergely, Catherine; Cottin, Yves

Keywords

BiomarkersBiomarqueursCardiometabolicCardiométaboliqueHumaninHumanineMitochondrial-derived-peptidesOxidative stressPeptides mitochondriauxStress oxydatif