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Brendan Miller, … , Kelvin Yen, Pinchas Cohen
Published May 2, 2022
Citation Information: J Clin Invest. 2022;132(9):e158449. https://doi.org/10.1172/JCI158449.
Citation Information: J Clin Invest. 2022;132(9):e158449. https://doi.org/10.1172/JCI158449.
Abstract
The mechanisms that explain mitochondrial dysfunction in aging and healthspan continue to be studied, but one element has been unexplored: microproteins. Small open reading frames in circular mitochondria DNA can encode multiple microproteins, called mitochondria-derived peptides (MDPs). Currently, eight MDPs have been published: humanin, MOTS-c, and SHLPs 1–6. This Review describes recent advances in microprotein discovery with a focus on MDPs. It discusses what is currently known about MDPs in aging and how this new understanding could add to the way we understand age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.
Authors
Brendan Miller, Su-Jeong Kim, Hiroshi Kumagai, Kelvin Yen, Pinchas Cohen
Citation information
Citations to this article (44)
| Title and authors | Publication | Year |
|---|---|---|
|
Mitochondrial diseases: from molecular mechanisms to therapeutic advances
Wen H, Deng H, Li B, Chen J, Zhu J, Zhang X, Yoshida S, Zhou Y |
Signal Transduction and Targeted Therapy | 2025 |
|
Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study
Zhu D, Wang Z, Li Y, Chen S, Kang X |
Journal of Orthopaedic Translation | 2025 |
|
Bioactive Glycyrrhizic Acid Ionic Liquid Self‐Assembled Nanomicelles for Enhanced Transdermal Delivery of Anti‐Photoaging Signal Peptides
Wang Z, Liu J, Chen Q, Wu Y, Li Y, Ou M, Tang S, Deng Z, Liu L, Jiang C, Zhu H, Liu Q, Yang B |
Advanced Science | 2025 |
|
HNGF6A ameliorates oxidative stress-mediated mitochondrial dysfunction in degenerative meniscus
Liu R, Du X, Chen Y, Zhu Z, Jiang Z, Zhang C, Jiang D, Zhang Z |
Bone & Joint Research | 2025 |
|
Impaired Expression of Humanin during Adrenocortical Carcinoma
Blatkiewicz M, Szyszka M, Olechnowicz A, Kamiński K, Jopek K, Komarowska H, Tyczewska M, Klimont A, Wierzbicki T, Karczewski M, Ruchała M, Rucinski M |
International journal of molecular sciences | 2024 |
|
Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
Zhang B, Chang JY, Lee MH, Ju SH, Yi HS, Shong M |
Diabetes & Metabolism Journal | 2024 |
|
The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions.
Lanfranchi M, Yandiev S, Meyer-Dilhet G, Ellouze S, Kerkhofs M, Dos Reis R, Garcia A, Blondet C, Amar A, Kneppers A, Polvèche H, Plassard D, Foretz M, Viollet B, Sakamoto K, Mounier R, Bourgeois CF, Raineteau O, Goillot E, Courchet J |
Nature Communications | 2024 |
|
Acod1 expression in cancer cells promotes immune evasion through the generation of inhibitory peptides
Schofield JH, Longo J, Sheldon RD, Albano E, Ellis AE, Hawk MA, Murphy S, Duong L, Rahmy S, Lu X, Jones RG, Schafer ZT |
Cell Reports | 2024 |
|
Mitochondrial DNA: Inherent Complexities Relevant to Genetic Analyses
Ferreira T, Rodriguez S |
Genes & development | 2024 |
|
A naturally occurring variant of SHLP2 is a protective factor in Parkinson’s disease
Kim SJ, Miller B, Hartel NG, Ramirez R II, Braniff RG, Leelaprachakul N, Huang A, Wang Y, Arpawong TE, Crimmins EM, Wang P, Sun X, Liu C, Levy D, Yen K, Petzinger GM, Graham NA, Jakowec MW, Cohen P |
Molecular Psychiatry | 2024 |
|
Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration
Kumagai H, Kim SJ, Miller B, Natsume T, Wan J, Kumagai ME, Ramirez R II, Lee SH, Sato A, Mehta HH, Yen K, Cohen P |
American journal of physiology. Endocrinology and metabolism | 2024 |
|
Socialized mitochondria: mitonuclear crosstalk in stress
Kim KH, Lee CB |
Experimental & molecular medicine | 2024 |
|
Renin–angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?
de Cavanagh EM, Inserra F, Ferder L |
Physiological Reports | 2024 |
|
Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology
Miller B, Kim S, Cao K, Mehta HH, Thumaty N, Kumagai H, Iida T, McGill C, Pike CJ, Nurmakova K, Levine ZA, Sullivan PM, Yen K, Ertekin\u2010Taner N, Atzmon G, Barzilai N, Cohen P |
Aging Cell | 2024 |
|
Mitochondria: fundamental characteristics, challenges, and impact on aging.
Liang R, Zhu L, Huang Y, Chen J, Tang Q |
Biogerontology | 2024 |
|
The mitochondrial stress signaling tunes immunity from a view of systemic tumor microenvironment and ecosystem
Kuo CL, Lin YC, Lo YK, Lu YZ, Babuharisankar AP, Lien HW, Chou HY, Lee AY |
iScience | 2024 |
|
MOTS-c modulates skeletal muscle function by directly binding and activating CK2
Kumagai H, Kim SJ, Miller B, Zempo H, Tanisawa K, Natsume T, Lee SH, Wan J, Leelaprachakul N, Kumagai ME, Ramirez R II, Mehta HH, Cao K, Oh TJ, Wohlschlegel JA, Sha J, Nishida Y, Fuku N, Dobashi S, Miyamoto-Mikami E, Takaragawa M, Fuku M, Yoshihara T, Naito H, Kawakami R, Torii S, Midorikawa T, Oka K, Hara M, Iwasaka C, Yamada Y, Higaki Y, Tanaka K, Yen K, Cohen P |
iScience | 2024 |
|
Inter- and intracellular mitochondrial communication: signaling hubs in aging and age-related diseases
Zhang M, Wei J, He C, Sui L, Jiao C, Zhu X, Pan X |
Cellular & Molecular Biology Letters | 2024 |
|
Mitochondrial Microproteins from Discovery to Function
Yen K, Miller B, Kumagai H, Silverstein A, Cohen P |
Trends in genetics : TIG | 2024 |
|
A tale of two pathways: Regulation of proteostasis by UPR(mt) and MDPs.
Johns A, Higuchi-Sanabria R, Thorwald MA, Vilchez D |
Current Opinion in Neurobiology | 2023 |
|
MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
Zheng Y, Wei Z, Wang T |
Frontiers in Endocrinology | 2023 |
|
Mitochondrial stress and mitokines in aging
Burtscher J, Soltany A, Visavadiya NP, Burtscher M, Millet GP, Khoramipour K, Khamoui AV |
Aging Cell | 2023 |
|
Novel Insights into Mitochondrial DNA: Mitochondrial Microproteins and mtDNA Variants Modulate Athletic Performance and Age-Related Diseases
Kumagai H, Miller B, Kim SJ, Leelaprachakul N, Kikuchi N, Yen K, Cohen P |
Genes & development | 2023 |
|
Humanin and Its Pathophysiological Roles in Aging: A Systematic Review
Coradduzza D, Congiargiu A, Chen Z, Cruciani S, Zinellu A, Carru C, Medici S |
Biology | 2023 |
|
Kidney-Related Function of Mitochondrial Protein Mitoregulin
Averina OA, Permyakov OA, Emelianova MA, Guseva EA, Grigoryeva OO, Lovat ML, Egorova AE, Grinchenko AV, Kumeiko VV, Marey MV, Manskikh VN, Dontsova OA, Vyssokikh MY, Sergiev PV |
International journal of molecular sciences | 2023 |
|
LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma
Meng K, Lu S, Li Y, Hu L, Zhang J, Cao Y, Wang Y, Zhang CZ, He Q |
EMBO reports | 2023 |
|
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
Kong BS, Lee C, Cho YM |
Diabetes & Metabolism Journal | 2023 |
|
Intranasal delivery of mitochondrial protein humanin rescues cell death and promotes mitochondrial function in Parkinson's disease
Kim KH |
Theranostics | 2023 |
|
Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension
Yousef H, Khandoker AH, Feng SF, Helf C, Jelinek HF |
Frontiers in Endocrinology | 2023 |
|
Brain Hydrophobic Peptides Antagonists of Neurotoxic Amyloid β Peptide Monomers/Oligomers–Protein Interactions
Gutierrez-Merino C |
International journal of molecular sciences | 2023 |
|
Current Advances in Mitochondrial Targeted Interventions in Alzheimer’s Disease
Sousa T, Moreira PI, Cardoso S |
Biomedicines | 2023 |
|
Acod1 Expression in Cancer Cells Promotes Immune Evasion through the Generation of Inhibitory Peptides
Schofield JH, Longo J, Sheldon RD, Albano E, Hawk MA, Murphy S, Duong L, Rahmy S, Lu X, Jones RG, Schafer ZT |
2023 | |
|
MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake—A Preliminary Study
Domin R, Pytka M, Żołyński M, Niziński J, Rucinski M, Guzik P, Zieliński J, Ruchała M |
International journal of molecular sciences | 2023 |
|
Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.
Xourafa G, Korbmacher M, Roden M |
Nature reviews. Endocrinology | 2023 |
|
Mitohormesis
Cheng YW, Liu J, Finkel T |
Cell Metabolism | 2023 |
|
Potential oxidative stress related targets of mitochondria-focused therapy of PTSD
Kmita H, Pinna G, Lushchak VI |
Frontiers in physiology | 2023 |
|
S14G-humanin confers cardioprotective effects against chronic adrenergic and pressure overload-induced heart failure in mice.
Zhao Q, Cai MM, Li D, Zhao BY, Zhou SS, Wu ZR, Shi YJ, Su L |
Heliyon | 2023 |
|
Micropeptides: origins, identification, and potential role in metabolism-related diseases.
Lu Y, Ran Y, Li H, Wen J, Cui X, Zhang X, Guan X, Cheng M |
Journal of Zhejiang University. Science. B | 2023 |
|
Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives
Karachaliou CE, Livaniou E |
Biology | 2023 |
|
Unique Properties of Apicomplexan Mitochondria
Lamb IM, Okoye IC, Mather MW, Vaidya AB |
Annual Review of Microbiology | 2023 |
|
Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities.
Li Y, Li Z, Ren Y, Lei Y, Yang S, Shi Y, Peng H, Yang W, Guo T, Yu Y, Xiong Y |
Journal of advanced research | 2023 |
|
Mitochondrial DNA: Consensuses and Controversies
Shokolenko I, Alexeyev M |
DNA | 2022 |
|
Circulating levels of MOTS-c in patients with breast cancer treated with metformin
Cuyàs E, Verdura S, Martin-Castillo B, Menendez JA |
Aging | 2022 |
|
Mitochondrial DNA variation in Alzheimer’s disease reveals a unique microprotein called SHMOOSE
Miller B, Kim SJ, Mehta HH, Cao K, Kumagai H, Thumaty N, Leelaprachakul N, Jiao H, Vaughan J, Diedrich J, Saghatelian A, Arpawong TE, Crimmins E, Ertekin-Taner N, Tubi MA, Hare ET, Braskie MN, Décarie-Spain L, Kanoski SE, Grodstein F, Bennett DA, Zhao L, Toga AW, Wan J, Yen K, Cohen P |
Molecular Psychiatry | 2022 |
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