The role of mitochondrial derived peptides (MDPs) in metabolism

Alis, Rafael; Lucía, Alejandro; Blesa, Rafael; Sanchís-Gomar, Fabián

doi:10.1002/jcp.25023

Cited by 20 publications

(17 citation statements)

References 10 publications

(14 reference statements)

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“…MOTS‐c shares many effects with metformin, a long‐standing first‐line antidiabetic drug, which is also known to act through activation of AMPK, emphasizing the potential therapeutic effect of MOTS‐c . MOTS‐c acts directly on muscle tissue, where are likely to exert the strongest possible effect on insulin‐resistance therapies, and avoid the liver toxicities induced by drugs such as metformin . For these reasons, MOTS‐c may be a novel potential treatment for obesity and T2DM, and may prove beneficial in future studies of specific patient populations.…”

Section: Discussionmentioning

confidence: 99%

“…If these findings in mice were found to be fully applicable to humans, this would open up the possibility of MOTS‐c treatment in human obesity and T2DM. It is a key challenge to confirm if MOTS‐c could be similarly regulated in humans and to determine its therapeutic potential . MOTS‐c profiles have not yet been reported in human obesity and T2DM.…”

Section: Introductionmentioning

confidence: 99%

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Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance

Zhang

et al. 2018

Pediatr Diabetes

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Background and Aims A novel bioactive peptide, mitochondrial‐derived peptide (MOTS‐c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS‐c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS‐c levels in obesity and explore the association between MOTS‐c levels and various metabolic parameters. Methods In this case‐control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017. Circulating MOTS‐c levels were measured, clinical data (eg, glucose, insulin, and lipid profile) were recorded, and anthropometric measurements were performed. Finally, we investigated correlations between MOTS‐c levels and related variables. Results MOTS‐c levels were significantly decreased in the obese group compared with the control group (472.61 ±22.83 vs 561.64 ±19.19 ng/mL, P <.01). After classification by sex, MOTS‐c levels were significantly decreased in obese male children and adolescents compared to their counterparts (465.26 ±24.53 vs 584.07 ±21.18 ng/mL, P <.001), while they were comparable between the obese and healthy female subjects (487.89 ±49.77 vs 508.85 ±38.76 ng/mL, P >.05). Further, MOTS‐c levels were negatively correlated with body mass index (BMI), BMI SD score, waist circumference, waist‐to‐hip ratio, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA‐IR), and glycated hemoglobin (HbA1c) in the male cohort. Conclusions Circulating MOTS‐c levels were decreased in obese male children and adolescents and correlated with markers of insulin resistance and obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance

Zhang

et al. 2018

Pediatr Diabetes

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“…Muscles secrete myokines, such as irisin [72] and musclin [73], in response to exercise that mediate inter-organ communication and coordination [74]. Although the effect of exercise on regulating MOTS-c production and secretion is unknown, its beneficial effects on HFD is mirrored by MOTS-c [75]. Further, MOTS-c increases cellular levels of AICAR (an AMPK agonist) and activates AMPK [4], a well-described regulator of exercise [76–78].…”

Section: Mitochondrial-derived Peptides (Mdps): a Newly Recognizedmentioning

confidence: 99%

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

Lee

Kim

Cohen

2016

Free Radical Biology and Medicine

142

129

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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.

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“…An emerging new class of mitochondrial signals capable of regulating aging and lifespan are the mitochondrial-derived peptides (MDPs), encoded by functional short open reading frames (sORFs) in the mtDNA [121]. Among them, Humanin (HN) is a recently identified neuroprotective and antiapoptotic peptide derived from a portion of the mitochondrial 16S ribosomal RNA, MT-RNR2 gene [122].…”

Section: Dietary Restriction Mitochondria Aging and Longevity Inmentioning

confidence: 99%

Dietary restriction, mitochondrial function and aging: from yeast to humans

Ruetenik¹,

Barrientos

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

121

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SUMMARY Dietary restriction (DR) attenuates many detrimental effects of aging and consequently promotes health and increases longevity across organisms. While over the last 15 years extensive research has been devoted towards understanding the biology of aging, the precise mechanistic aspects of DR are yet to be settled. Abundant experimental evidence indicates that the DR effect on stimulating health impinges several metabolic and stress-resistance pathways. Downstream effects of these pathways include a reduction in cellular damage induced by oxidative stress, enhanced efficiency of mitochondrial functions and maintenance of mitochondrial dynamics and quality control, thereby attenuating age-related declines in mitochondrial function. However, the literature also accumulates conflicting evidence regarding how DR ameliorates mitochondrial performance and whether that is enough to slow age-dependent cellular and organismal deterioration. Here, we will summarize the current knowledge about how and to which extent the influence of different DR regimes on mitochondrial biogenesis and function contribute to postpone the detrimental effects of aging on healthspan and lifespan.

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The role of mitochondrial derived peptides (MDPs) in metabolism

Cited by 20 publications

References 10 publications

Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance

Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance

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

Dietary restriction, mitochondrial function and aging: from yeast to humans

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