bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2026–09–27
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. SIM2s coordinates programmed mitophagy with respiratory chain supercomplex remodeling during mammary epithelial differentiation.
  2. Mitotic assembly of respiratory supercomplexes ensures accurate cell division and fuels tumor growth.
  1. bioRxiv. 2026 Sep 20. pii: 2026.09.14.750442. [Epub ahead of print]
    SIM2s coordinates programmed mitophagy with respiratory chain supercomplex remodeling during mammary epithelial differentiation.
    Ramsey M Jenschke, Madelyn Spooner-Harris, Steven W Wall, Lilia Sanchez, Jessica Epps, Sophia Schutmaat, Kaitlin P Kelly, Tyler Frey, Monique Rijnkels, Weston W Porter.
      Lactation requires mammary epithelial cells (MECs) to rapidly expand mitochondrial function while remodeling the mitochondrial population that supports milk synthesis and secretion. Programmed mitophagy is required for MEC differentiation, yet why mitochondrial turnover is necessary during this developmental transition remains poorly understood. Using Mito-QC reporter mice, we identified developmentally regulated changes in mitolysosome burden across the transition from late pregnancy to lactation that were altered by mammary-specific gain or loss of the bhlh/PAS protein, SIM2s (single-minded 2 s). In differentiating HC11 cells, mitochondrial turnover was accompanied by increased assembly and activity of respiratory supercomplexes containing complexes I, III, and IV. Depletion of PRKN prevented acquisition of this differentiation-associated respiratory profile and impaired lactogenic differentiation. SIM2s co-migrated with higher-order respiratory assemblies, and loss of SIM2s reduced supercomplex assembly and activity in HC11 cells and mammary tissue. SIM2s also localized in close proximity to complex III in differentiated mammary epithelium, whereas loss of SIM2s reduced proximity between complexes III and IV. Together, these findings support a model in which SIM2s coordinates PRKN-dependent mitochondrial turnover with respiratory-chain remodeling during MEC differentiation. Our results suggest that programmed mitophagy does more than remove mitochondria during development; it contributes to establishment of a mitochondrial population with a respiratory-chain architecture suited to the emerging differentiated state.
    DOI:  https://doi.org/10.64898/2026.09.14.750442
  2. EMBO Rep. 2026 Sep 23.
    Mitotic assembly of respiratory supercomplexes ensures accurate cell division and fuels tumor growth.
    Ting Wang, Aoxing Cheng, Lingyu Kong, Weiyi You, Jihua Liu, Xing Liu, Xuebiao Yao, Yi Yang, Yuzheng Zhao, Weiwei Yang, Kaiguang Zhang, Zhenye Yang, Jing Guo.
      As cells progress from interphase into mitosis, fluctuating metabolic demands coincide with mitochondrial fission. However, the mechanisms by which mitochondria coordinate morphological changes and metabolic adjustments during mitosis remain poorly understood. Using proteomic analysis of BN-PAGE fractions, we show that assembly of the mitochondrial respiratory supercomplexes, comprising electron transport chain complexes I, III, and IV, is markedly enhanced during mitosis in HeLa and MDA-MB-468 cancer cells. Mechanistically, the upregulation of specific CI subunits, including NDUFA3, drives the modular assembly of supercomplexes in mitosis. We further demonstrate that CDK1 promotes the translation of NDUFA3 to enable supercomplex formation. Disruption of this process impairs mitochondrial integrity, energy production, and redox homeostasis, leading to ROS accumulation that triggers mitotic cell death and chromosome segregation defects across multiple models. Importantly, inhibiting mitotic supercomplex assembly induces chromosome mis‑segregation and suppresses tumor growth in vivo. Our findings reveal supercomplex assembly as a key mechanism coordinating mitochondrial fission with metabolic adaptation to support cell division and tumor proliferation in these cancer cell contexts.
    DOI:  https://doi.org/10.1038/s44319-026-00937-8
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