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MOTS-c research studies: evidence explorer
Search and filter indexed MOTS-c publications by model, substance, species, pathway, research area and evidence tier. Every record links to PubMed.
By the MOTS-C Peptide editorial teamLast reviewed Sources: editorial review pending
Short answer
253 MOTS-c publications are indexed here: 184 primary studies and 69 reviews. Each record states what kind of system was studied, whether MOTS-c was given or measured, what was reported and what the study’s own limitations were. Filter below, or read the methodology first.
Search and filters are reflected in the page address, so any view you build can be shared or cited. Selecting two to four records opens them in the side-by-side comparison.
| Study | Model | What was reported | Limitations | Tier |
|---|---|---|---|---|
| Li 2027 Bioact Mater MOTS-c analogue or derivative | Animal MOTS-c conjugated to a self-assembling Q11 peptide as a hydrogel carrier for isolated mitochondria; rat myocardial infarction model and macrophages | Reported that a MOTS-c-Q11 peptide hydrogel extended the survival and enzyme activity of isolated mitochondria and increased their internalisation by macrophages through an AMPK-dependent mechanism. Reported that in a rat myocardial infarction model the combined system was associated with less M1 macrophage infiltration, less cardiomyocyte damage and improved cardiac function and remodelling. | MOTS-c is used as part of a conjugated biomaterial rather than as the free peptide, so its independent contribution is hard to isolate; group sizes not reported in the abstract; a single rat infarction model with short follow-up. | Evidence tier C |
| Wang 2026 Front Immunol MOTS-c administered | Analytical Bulk and single-cell transcriptomics of a murine chronic radiation proctitis model with virtual screening and molecular dynamics | Reported that an Ms4a6c-expressing macrophage subpopulation was associated with pro-fibrotic programmes in a murine radiation proctitis model and in human liver cirrhosis and pulmonary fibrosis datasets. Reported that molecular docking and dynamics simulations ranked MOTS-c as a top candidate predicted to bind Ms4a6c, with no experimental testing of MOTS-c. | MOTS-c involvement is entirely computational, with no binding assay or in vivo testing; the authors state experimental validation is pending; single murine model underlies the primary transcriptomics. | Evidence tier D |
| Zhang 2026 Antioxidants (Basel) Endogenous MOTS-c measured | Human obs. Healthy young males stratified as elite track and field athletes, recreationally active and sedentary; serum MOTS-c and fitness testing | Measured progressively higher serum MOTS-c from sedentary to recreationally active to elite athlete groups of young males. Reported strong positive correlations of serum MOTS-c with peak oxygen uptake, superoxide dismutase, back muscle endurance and post-fatigue force, a strong inverse correlation with post-exercise malondialdehyde, and no significant correlation with handgrip strength. | Very small groups of 10 young males each; cross-sectional design precludes causal inference; multiple strong correlations in a small sample risk overfitting. | Evidence tier B |
| Li 2026 Cell Commun Signal Several | Animal Maternal serum and placental tissue from intrahepatic cholestasis of pregnancy; cholic acid-induced mouse model; taurocholic acid-exposed HUVECs | Measured lower MOTS-c in maternal serum and placental tissue from patients with intrahepatic cholestasis of pregnancy. Reported that in cholic acid-exposed mice, administered MOTS-c was associated with more placental angiogenesis, less endothelial apoptosis and higher birth weight, placental efficiency and neonatal survival, and that MOTS-c bound BACH1 and promoted its K33-linked ubiquitination and degradation, with BACH1 overexpression abolishing the effect in human umbilical vein endothelial cells. | Clinical sample sizes not reported in the abstract; a single chemically induced mouse model of cholestasis and one endothelial cell type; mechanism rests on overexpression rather than placental genetic deletion. | Evidence tier C |
| Wang 2026 Biochem Pharmacol MOTS-c administered | Animal db/db mice with diabetic nephropathy and HK-2 human proximal tubular cells with LARS1 overexpression | Reported that administered MOTS-c was associated with preserved urinary albumin-to-creatinine ratio, less tubular injury, less lipid deposition and less macrophage accumulation in db/db mice. Reported lower p16, gammaH2AX and SA-beta-gal signal and lower LARS1 with increased LC3-mediated lipid droplet clearance, with LARS1 overexpression in HK-2 cells and an autophagy inhibitor in mice reversing these changes. | Group sizes and sex not reported in the abstract; a single genetic diabetes model and one human tubular cell line; mechanism relies on a non-selective autophagy inhibitor. | Evidence tier C |
| Tsui 2026 Reprod Fertil MOTS-c administered | Cells Aging-associated HGL5 human granulosa cells, ex vivo oocytes from young and aged mice, and public ovarian transcriptomic datasets | Reported that MOTS-c increased mitochondrial mass, ATP-linked and maximal respiration and spare respiratory capacity and reduced proton leak in aging-associated human granulosa cells without increasing reactive oxygen species. Reported that ex vivo MOTS-c exposure increased first polar body positivity and mitochondria-associated fluorescence and lowered oxidative-stress fluorescence in aged mouse oocytes, though outcomes stayed below young-reference levels. | A single immortalised granulosa cell line plus ex vivo mouse oocytes, with replicate numbers not reported in the abstract; fertilisation, embryo development and live birth were not assessed; transcriptomic component is a reanalysis of public datasets. | Evidence tier D |
| Niinuma 2026 Cells MOTS-c administered | Review Narrative review of mitochondria-endoplasmic reticulum crosstalk in pancreatic beta-cell stress | Reviewed endoplasmic reticulum-mitochondria crosstalk in pancreatic beta-cell failure in type 2 diabetes and listed MOTS-c among strategies discussed as targeting this interface, contrasting rodent and human data. | Narrative review without systematic search; MOTS-c is mentioned only in passing as a candidate, with no appraisal of the supporting studies. | Evidence tier R |
| Rostami 2026 Tissue Cell Related mitochondrial peptide | Review Hypothesis-driven review of mitochondrial-derived peptides in female reproduction, covering MOTS-c, humanin and SHLP2 | Reviewed evidence that MOTS-c, humanin and SHLP2 decline with age in humans alongside declining oocyte quality, and cited a reported reduction in serum MOTS-c in polycystic ovary syndrome as preliminary and unreplicated. Proposed that MDP levels in follicular fluid and granulosa cells be measured directly to test biomarker potential in assisted reproduction. | Hypothesis-driven review rather than primary data; the authors note that the key MOTS-c clinical link is unreplicated and lacks ovarian sampling. | Evidence tier R |
| Kurian 2026 J Bioenerg Biomembr Related mitochondrial peptide | Review Narrative review of mitokines in cardiovascular disease, covering FGF21, GDF15, humanin and MOTS-c | Reviewed mitokine signalling in cardiovascular stress, grouping MOTS-c and humanin with FGF21 and GDF15, and proposed a framework in which mitokine identity, pattern and timing convey information about mitochondrial stress. Noted that mechanistic uncertainty remains particularly large for the mitochondrial-derived peptides. | Narrative review without systematic search; MOTS-c is covered as one of several mitokines and the authors state its mechanisms are not established. | Evidence tier R |
| Suliman 2026 Antioxidants (Basel) Related mitochondrial peptide | Human obs. Adults with kidney failure undergoing living-donor kidney transplantation and controls; serum AGEs, RAGE isoforms and MDPs by ELISA | Measured higher advanced glycation end-products and lower mitochondrial-derived peptides, including MOTS-c, in adults with chronic kidney disease compared with controls. Reported that MOTS-c was inversely associated with advanced glycation end-products and with the AGEs/sRAGE ratio, while humanin was independently associated with AGEs and sRAGE measures. | Cross-sectional design with MOTS-c one of several peptides measured; single-centre transplantation cohort; ELISA-based peptide quantification without orthogonal confirmation. | Evidence tier B |
| Ayubi 2026 Physiol Int Endogenous MOTS-c measured | Review Systematic review of nine studies on exercise and mitochondrial-derived peptide levels, including MOTS-c | Systematically reviewed nine studies of exercise and mitochondrial-derived peptides including MOTS-c, and reported that most described a trend toward higher MDP levels after exercise. The authors noted that the small number of studies and variation in design, participants and exercise protocols limit interpretation. | Only nine heterogeneous studies were included, with no meta-analysis or formal risk-of-bias grading reported in the abstract; human data were described as particularly limited. | Evidence tier R |
| Zhao 2026 Eur J Pharmacol Several | Review Narrative review of MOTS-c in sepsis-induced cardiomyopathy | Reviewed MOTS-c biology in relation to sepsis-induced cardiomyopathy, distinguishing direct evidence in that setting from findings extrapolated from other cardiovascular, metabolic and inflammatory models. Concluded that direct sepsis-induced cardiomyopathy evidence for MOTS-c is limited and that several proposed mechanisms were established in other settings. | Narrative review without systematic search; the authors note sparse disease-specific data and unresolved pharmacokinetic and biodistribution questions under septic conditions. | Evidence tier R |
| Rice 2026 Elife Several | Animal Mouse model of acute MRSA peritonitis; human monocytes and primary mouse monocyte differentiation; bacterial membrane assays | Reported that MOTS-c is an amphipathic, cationic mitochondrially encoded peptide with direct antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus, in part by targeting bacterial membranes, and that it neutralised MRSA infectivity in a mouse peritonitis model. Reported that interferon gamma, lipopolysaccharide and differentiation signals induced endogenous MOTS-c in human monocytes and that exogenous MOTS-c reprogrammed mouse monocytes into macrophages with antigen-presentation and interferon signatures and enhanced bacterial clearance. | Group sizes not reported in the abstract; acute single-organism infection model; in vitro peptide exposure is supraphysiological relative to measured circulating levels. | Evidence tier C |
| Li 2026 Front Immunol MOTS-c administered | Review Narrative review of mitochondrial dysfunction in acute respiratory distress syndrome | Reviewed mitochondrial dysfunction and glycolytic reprogramming in acute respiratory distress syndrome and listed MOTS-c among mitochondria-targeted agents reported to show promise in preclinical models. | Narrative review without systematic search; MOTS-c is mentioned only as one candidate agent among many, with no appraisal of the underlying studies. | Evidence tier R |
| Mustafa 2026 Epigenomics Related mitochondrial peptide | Review Narrative review of short open reading frame-encoded microproteins, MOTS-c among the examples | Reviewed the classification, discovery and regulation of short open reading frame-encoded microproteins and cited MOTS-c alongside humanin, myoregulin and others as examples of microproteins implicated in cardiometabolic disease, neurodegeneration and cancer. | Narrative review with no systematic search; MOTS-c appears as one illustrative example rather than a focus, so no appraisal of the MOTS-c evidence base is given. | Evidence tier R |
| Horwath 2026 Exp Physiol Endogenous MOTS-c measured | Human obs. Adults with cerebral palsy using running frames and typically developing adults and adolescents; plasma MDPs before and after endurance exercise | Measured plasma MOTS-c, humanin and SHMOOSE in adults with cerebral palsy and typically developing participants and found comparable basal levels despite lower muscle mass and peak oxygen uptake in the cerebral palsy group. Reported no or only modest changes in circulating MDPs after an acute endurance exercise bout, with no differences between groups. | Small group sizes not reported in the abstract; single post-exercise sampling point; in-house ELISA without external validation and heterogeneous exercise modes between groups. | Evidence tier B |
| Xing 2026 Inflamm Regen Several | Cells Adipose-derived mesenchymal stromal cells from donors with obesity and lean donors; MOTS-c-pretreated cells delivered to stenotic mouse kidneys | Measured lower basal MOTS-c expression in mesenchymal stromal cells from donors with obesity, and reported that MOTS-c co-incubation restored intracellular levels and activated AMPK but reduced proliferation and increased p16, p21 and TNF-alpha expression. Reported that MOTS-c-pretreated cells failed to improve renal perfusion, fibrosis or tubular injury in mice with renal artery stenosis, and that pretreatment also blunted the effect of lean-donor cells. | Small donor numbers per group; a single cell type and one murine renal stenosis model; effects assessed after in-culture exposure rather than systemic administration. | Evidence tier D |
| Mills 2026 Exp Physiol MOTS-c administered | Animal Male Sprague-Dawley rats with high-fat diet and streptozotocin-induced type 2 diabetes | Reported that administered MOTS-c was associated with lower fasting blood glucose and circulating C-reactive protein and with selective changes in plasma IL-10 and IL-1beta in diabetic rats. Reported lower NLRP3, ASC and cleaved caspase-1 staining in left ventricular tissue after MOTS-c administration. | Male rats only in a single chemically induced diabetes model, with group sizes not reported in the abstract; immunohistochemistry is semi-quantitative and no cardiac functional endpoints were reported. | Evidence tier C |
| Sonay 2026 J Clin Med Endogenous MOTS-c measured | Human obs. Patients with Hashimoto's thyroiditis and age- and sex-matched healthy controls; circulating MOTS-c | Measured lower circulating MOTS-c in patients with Hashimoto's thyroiditis than in matched controls, with inverse correlations with body mass index, fasting glucose, HbA1c, HOMA-IR, thyroid-stimulating hormone, C-reactive protein and thyroid autoantibodies. Reported that Hashimoto's thyroiditis and HOMA-IR were independent determinants of lower MOTS-c in regression analysis. | Cross-sectional design cannot establish direction; single-centre sample measured by ELISA at one time point; medication and iodine status largely unaccounted for beyond levothyroxine use. | Evidence tier B |
| Jamnick 2026 Front Med (Lausanne) MOTS-c administered | Animal Male mice bearing Colon-26 carcinoma; differentiated myotubes in culture | Reported that tumour-bearing mice lost body weight and that administered MOTS-c was not associated with preservation of total body weight or fat mass but was associated with preserved quadriceps mass, with a trend for gastrocnemius mass and EDL function. Reported attenuated Atrogin-1 and MuRF1 upregulation, increased inhibitory pFOXO1, reduced pFOXO3a and partial restoration of PGC-1alpha in muscle, and increased PGC-1alpha mRNA and AMPK phosphorylation in myotubes. | Male mice in a single aggressive tumour cachexia model with group sizes not reported in the abstract; effects were partial and some endpoints only trended; survival and function were assessed narrowly. | Evidence tier C |