Mitochondrially derived peptides as novel regulators of metabolism

Abstract

Mitochondrially derived peptides represent a new class of circulating signalling molecules. Humanin, the first member of this class, has been shown to have several metabolic effects such as reducing weight gain and visceral fat and increasing glucose-stimulated insulin release. The discovery of several other new members, such as MOTS-c and SHLP1-6, has further added to this group. These new peptides have also been found to affect metabolism with MOTS-c potently decreasing weight gain in mice on a high-fat diet. This review covers the basic biology of this class of peptides and discusses the relevance to organismal metabolism.

Keywords: insulin; metabolism; mitochondria; neuroendocrine; oxidative metabolism.

Figure 1. The human mitochondrial genome

Relative locations of genes are represented as coloured blocks including humanin (red), MOTS‐c (yellow), SHLP2 and SHLP3 (pink and magenta, respectively). Twenty‐two tRNAs encoded from mitochondria are represented as green stars. Potential epigenetic modulation CpG sites in the mtDNA are marked in brown and the coordinates were obtained from Yu et al. 2017.

Figure 2. MDP signalling

Schematic illustration of humanin‐, MOTS‐c‐ and SHLP‐mediated signalling pathways and biological functions. MEK, mitogen‐activated protein kinase kinase; PI3K, phosphoinositide 3‐kinase.