Mitochondrial-Derived Peptides in Diabetes and Its Complications

Wu, Ying; Sun, Lijie; Zhuang, Zhoudao; Hu, Xiaoqing; Dong, Delu

doi:10.3389/fendo.2021.808120

Cited by 17 publications

(18 citation statements)

References 61 publications

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“…MOTS-c has also been found to be involved in the regulation of nuclear gene expression by binding to transcription factors ( 5 , 19 , 24 ). Under resting conditions, MOTS-c is mainly distributed in the mitochondria outside the nucleus ( 5 , 7 , 19 ).…”

Section: Physiological Function Of Mots-cmentioning

confidence: 99%

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

2023

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Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. The MOTS-c protein is transferred to the nucleus during metabolic stress and directs the expression of nuclear genes to promote cell balance. Different tissues co-expressed the protein with mitochondria, and plasma also contained the protein, but its level decreased with age. In addition, MOTS-c has been shown to improve glucose metabolism in skeletal muscle, which indicates its benefits for diseases such as diabetes, obesity, and aging. Nevertheless, MOTS-c has been used less frequently in disease treatment, and no effective method of applying MOTS-c in the clinic has been developed. Throughout this paper, we discussed the discovery and physiological function of mitochondrial-derived polypeptide MOTS-c, and the application of MOTS-c in the treatment of various diseases, such as aging, cardiovascular disease, insulin resistance, and inflammation. To provide additional ideas for future research and development, we tapped into the molecular mechanisms and therapeutic potentials of MOTS-c to improve diseases and combined the technology with synthetic biology in order to offer a new approach to its development and application.

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Section: Physiological Function Of Mots-cmentioning

confidence: 99%

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

2023

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“…Diabetes is spreading at the rapid rate around the world, and its complications are a leading cause of death [ 50 , 51 ]. Oxidative stress is a critical factor in the development, progression, and consequences of diabetes [ 51 ].…”

Section: What Are Mitochondrial Derived Peptides (Mdps)?mentioning

confidence: 99%

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases

Mohtashami

Singh

Salimiaghdam

et al. 2022

IJMS

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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.

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“…One of the first MDPs described was the mitochondrial open reading frame of 12s rRNA-c (MOTS-c), between positions 642 and 1888 of the sequence located within 51 bp of the region that codes for the mitochondrial ribosomal small sub-unit on the MT-RNR1 gene. MT-RNR1 transcribes for a peptide consisting of 16 amino acids with a structure similar to adiponectin, which has been implicated in the regulation of insulin sensitivity and metabolic homeostasis, with a special main action in muscle tissue [23].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial-derived Peptide Single-nucleotide Polymorphisms Associated with Cardiovascular Complications in Type 2 Diabetes

Gaona¹,

Gregorio²,

Jiménez³

et al. 2022

Preprint

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Since the discovery of mitochondrial-derived peptides (MDP), their participation in cellular metabolism is no longer considered as the sole function of the mitochondria, but importance was also attached to its role as a source of protective factors of metabolic stress. These peptides are encoded in the mitochondrial genome and translated into the mitochondria or cytoplasm, to signal within the cell or be released and bind to membrane receptors. The objective of this work was explored and compare the frequency of MT-RNR1 and MT-RNR2 variants in sequences obtained from T2D individuals and control population. 213 different mitochondrial polymorphisms previously reported in the literature associated with T2D and cardiovascular diseases were analyzed. We can found three variants in the MT-RNR1 not related with MOTS-c coding sequence: m.1189T>C (rs28358571), m.1420T>C (rs111033356), and m.1438A>G (rs2001030); and secondly, three polymorphisms associated to MT-RNR2 m.2667T>C (rs878870626) related to humanin, m.1811A>G (rs28358576) in SHPL3 and m.3027T>C (rs199838004) in SHPL6 associated with statistical differences between the T2D and control group. All these findings were previously related to cardiovascular complications in literature and, as far as we know, relating for the first time in diabetic patients.

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Mitochondrial-Derived Peptides in Diabetes and Its Complications

Cited by 17 publications

References 61 publications

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases

Mitochondrial-derived Peptide Single-nucleotide Polymorphisms Associated with Cardiovascular Complications in Type 2 Diabetes

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