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Free Radic Biol Med. 2016 Nov;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. Epub 2016 May 20.

MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.

Author information

1
USC Leonard Davis School of Gerontology, 3715 McClintock Ave., Suite 103, Los Angeles, CA 90089, United States. Electronic address: changhan.lee@usc.edu.
2
USC Leonard Davis School of Gerontology, 3715 McClintock Ave., Suite 103, Los Angeles, CA 90089, United States.
3
USC Leonard Davis School of Gerontology, 3715 McClintock Ave., Suite 103, Los Angeles, CA 90089, United States. Electronic address: hassy@usc.edu.

Abstract

Mitochondria are ancient organelles that are thought to have emerged from once free-living α-proto-bacteria. As such, they still possess several bacterial-like qualities, including a semi-autonomous genetic system, complete with an independent genome and a unique genetic code. The bacterial-like circular mitochondrial DNA (mtDNA) has been described to encode 37 genes, including 22 tRNAs, 2 rRNAs, and 13 mRNAs. Two additional peptides reported to originate from the mtDNA, namely humanin (Hashimoto et al., 2001; Ikone et al., 2003; Guo et al., 2003) [1-3] and MOTS-c (mitochondrial ORF of the twelve S c) (Lee et al., 2015) [4], indicate a larger mitochondrial genetic repertoire (Shokolenko and Alexeyev, 2015) [5]. These mitochondrial-derived peptides (MDPs) have profound and distinct biological activities and provide a paradigm-shifting concept of active mitochondrial-encoded signals that act at the cellular and organismal level (i.e. mitochondrial hormone) (da Cunha et al., 2015; Quiros et al., 2016) [6,7]. Considering that mitochondria are the single most important metabolic organelle, it is not surprising that these MDPs have metabolic actions. MOTS-c has been shown to target the skeletal muscle and enhance glucose metabolism. As such, MOTS-c has implications in the regulation of obesity, diabetes, exercise, and longevity, representing an entirely novel mitochondrial signaling mechanism to regulate metabolism within and between cells.

KEYWORDS:

Aging; Exercise; Fat; Insulin; MOTS-c; Metabolism; Mitochondrial-derived peptides; Muscle

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