Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA.
Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA 92697, USA.
Int J Mol Sci. 2022 Oct 9;23(19):11991. doi: 10.3390/ijms231911991.
MOTS-c, a 16 amino acid mitochondrial derived peptide, is encoded from the 12S rRNA region of the mitochondrial genome. Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction. It is colocalized to mitochondria in various tissues and is found in plasma, but the levels decline with age. Since MOTS-c has important cellular functions as well as a possible hormonal role, it has been shown to have beneficial effects on age-related diseases including Diabetes, Cardiovascular diseases, Osteoporosis, postmenopausal obesity and Alzheimer. Aging is characterized by gradual loss of (mitochondrial) metabolic balance, decreased muscle homeostasis and eventual diminished physical capability, which potentially can be reversed with MOTS-c treatment. This review examines the latest findings on biological effects of MOTS-c as a nuclear regulatory peptide and focuses on the role of MOTS-c in aging and age-related disorders, including mechanisms of action and therapeutic potential.
MOTS-c 是一种 16 个氨基酸的线粒体衍生肽,由线粒体基因组的 12S rRNA 区域编码。在应激条件下,MOTS-c 易位到细胞核,在那里它可以响应代谢功能障碍调节广泛的基因。它在各种组织中与线粒体共定位,并存在于血浆中,但随着年龄的增长而下降。由于 MOTS-c 具有重要的细胞功能以及可能的激素作用,它已被证明对包括糖尿病、心血管疾病、骨质疏松症、绝经后肥胖和阿尔茨海默病在内的与年龄相关的疾病具有有益的影响。衰老的特征是(线粒体)代谢平衡逐渐丧失、肌肉内稳态下降以及最终身体机能下降,而 MOTS-c 治疗可能会逆转这些现象。这篇综述考察了 MOTS-c 作为核调节肽的最新生物学效应发现,并重点关注了 MOTS-c 在衰老和与年龄相关的疾病中的作用,包括作用机制和治疗潜力。