ArticleProceedings of the National Academy of Sciences of the United States of America2022
The cardiac-enriched microprotein mitolamban regulates mitochondrial respiratory complex assembly and function in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.Frontiers in immunology · 2026Pooled it
- STREMI: a dual-function upstream ORF-encoded regulator of mitochondrial cristae architecture.EMBO reports · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- MENTSH: A novel mitochondrial microprotein linked to a SNP associated with type 2 diabetes.Theranostics · 2026Article
- Microproteins in Metabolic Biology: Emerging Functions and Potential Roles as Nutrient-Linked Biomarkers.International journal of molecular sciences · 2025Review
- Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice.Science advances · 2025Article
- Microproteins in Metabolism.Cells · 2025Review
- Emerging roles for microproteins as critical regulators of endoplasmic reticulum function and cellular homeostasis.Seminars in cell & developmental biology · 2025Review
- TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy.Journal of endocrinological investigation · 2025Article
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Pathological variants in nuclear genes causing mitochondrial complex III deficiency: An update.Journal of inherited metabolic disease · 2024Review
- Noncanonical microprotein regulation of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Micropeptides: origins, identification, and potential role in metabolism-related diseases.Journal of Zhejiang University. Science. B · 2023Review
- Mitochondrial microproteins: critical regulators of protein import, energy production, stress response pathways, and programmed cell death.American journal of physiology. Cell physiology · 2023Review
- Article
- Review
- LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma.EMBO reports · 2023Article
- Proteoforms expand the world of microproteins and short open reading frame-encoded peptides.iScience · 2023Review
- A lncRNA-encoded mitochondrial micropeptide exacerbates microglia-mediated neuroinflammation in retinal ischemia/reperfusion injury.Cell death & disease · 2023Article
- Micropeptide hetero-oligomerization adds complexity to the calcium pump regulatory network.Biophysical journal · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Emerging evidence indicates that a subset of RNA molecules annotated as noncoding contain short open reading frames that code for small functional proteins called microproteins, which have largely been overlooked due to their small size. To search for cardiac-expressed microproteins, we used a comparative genomics approach and identified mitolamban (Mtlbn) as a highly conserved 47-amino acid transmembrane protein that is abundantly expressed in the heart. Mtlbn localizes specifically to the inner mitochondrial membrane where it interacts with subunits of complex III of the electron transport chain and with mitochondrial respiratory supercomplexes. Genetic deletion of Mtlbn in mice altered complex III assembly dynamics and reduced complex III activity. Unbiased metabolomic analysis of heart tissue from Mtlbn knockout mice further revealed an altered metabolite profile consistent with deficiencies in complex III activity. Cardiac-specific Mtlbn overexpression in transgenic (TG) mice induced cardiomyopathy with histological, biochemical, and ultrastructural pathologic features that contributed to premature death. Metabolomic analysis and biochemical studies indicated that hearts from Mtlbn TG mice exhibited increased oxidative stress and mitochondrial dysfunction. These findings reveal Mtlbn as a cardiac-expressed inner mitochondrial membrane microprotein that contributes to mitochondrial electron transport chain activity through direct association with complex III and the regulation of its assembly and function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.