ArticleExperimental & molecular medicine2023
Noncanonical role of singleminded-2s in mitochondrial respiratory chain formation in breast cancer.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.eLife · 2026Article
- Integrative epitranscriptomic and transcriptomic characterization in human colorectal cancer.Journal of advanced research · 2026Article
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- Loss of STING impairs lactogenic differentiation.Development (Cambridge, England) · 2024Article
- Non-Genomic Hallmarks of Aging-The Review.International journal of molecular sciences · 2023Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulation of cellular metabolism is a hallmark of breast cancer progression and is associated with metastasis and therapeutic resistance. Here, we show that the breast tumor suppressor gene SIM2 promotes mitochondrial oxidative phosphorylation (OXPHOS) using breast cancer cell line models. Mechanistically, we found that SIM2s functions not as a transcription factor but localizes to mitochondria and directly interacts with the mitochondrial respiratory chain (MRC) to facilitate functional supercomplex (SC) formation. Loss of SIM2s expression disrupts SC formation through destabilization of MRC Complex III, leading to inhibition of electron transport, although Complex I (CI) activity is retained. A metabolomic analysis showed that knockout of SIM2s leads to a compensatory increase in ATP production through glycolysis and accelerated glutamine-driven TCA cycle production of NADH, creating a favorable environment for high cell proliferation. Our findings indicate that SIM2s is a novel stabilizing factor required for SC assembly, providing insight into the impact of the MRC on metabolic adaptation and breast cancer progression.
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Registered trials
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