Schägger, H. & Pfeiffer, K. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J. 19, 1777–1783 (2000).

Article  PubMed  PubMed Central  Google Scholar 

Gu, J. et al. The architecture of the mammalian respirasome. Nature 537, 639–643 (2016).

Article  CAS  PubMed  Google Scholar 

Letts, J. A., Fiedorczuk, K. & Sazanov, L. A. The architecture of respiratory supercomplexes. Nature 537, 644–648 (2016).

Article  CAS  PubMed  Google Scholar 

Wu, M., Gu, J., Guo, R., Huang, Y. & Yang, M. Structure of mammalian respiratory supercomplex I1III2IV1. Cell 167, 1598–1609.e10 (2016).

Article  CAS  PubMed  Google Scholar 

Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M. & Sazanov, L. A. Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Mol. Cell 75, 1131–1146.e6 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vercellino, I. & Sazanov, L. A. Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Nature 598, 364–367 (2021).

Article  CAS  PubMed  Google Scholar 

Guo, R., Zong, S., Wu, M., Gu, J. & Yang, M. Architecture of human mitochondrial respiratory megacomplex I2III2IV2. Cell 170, 1247–1257 (2017).

Article  CAS  PubMed  Google Scholar 

Sousa, J. S., Mills, D. J., Vonck, J. & Kühlbrandt, W. Functional asymmetry and electron flow in the bovine respirasome. eLife 5, e21290 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Protasoni, M. et al. Respiratory supercomplexes act as a platform for complex III‐mediated maturation of human mitochondrial complexes I and IV. EMBO J. 39, e102817 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lobo‐Jarne, T. et al. Multiple pathways coordinate assembly of human mitochondrial complex IV and stabilization of respiratory supercomplexes. EMBO J. 39, e103912 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Diaz, F., Fukui, H., Garcia, S. & Moraes, C. T. Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts. Mol. Cell. Biol. 26, 4872–4881 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schägger, H. et al. Significance of respirasomes for the assembly/stability of human respiratory chain complex I. J. Biol. Chem. 279, 36349–36353 (2004).

Article  PubMed  Google Scholar 

Ikeda, K. et al. Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance. Nat. Commun. 10, 1–15 (2019).

Article  Google Scholar 

Wang, G., Popovic, B., Tao, J. & Jiang, A. Overexpression of COX7RP promotes tumor growth and metastasis by inducing ROS production in hepatocellular carcinoma cells. Am. J. Cancer Res 10, 1366–1383 (2020).

CAS  PubMed  PubMed Central  Google Scholar 

Hollinshead, K. E. R. et al. Respiratory supercomplexes promote mitochondrial efficiency and growth in severely hypoxic pancreatic cancer. Cell Rep. 33, 108231 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rohlenova, K. et al. Selective disruption of respiratory supercomplexes as a new strategy to suppress Her2high breast cancer. Antioxid. Redox Signal 26, 84–103 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Antoun, G. et al. Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals. Diabetologia 58, 2861–2866 (2015).

Article  CAS  PubMed  Google Scholar 

Huertas, J. R., Al Fazazi, S., Hidalgo-Gutierrez, A., López, L. C. & Casuso, R. A. Antioxidant effect of exercise: exploring the role of the mitochondrial complex I superassembly. Redox Biol. 13, 477–481 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Greggio, C. et al. Enhanced respiratory chain supercomplex formation in response to exercise in human skeletal muscle. Cell Metab. 25, 301–311 (2017).

Article  CAS  PubMed  Google Scholar 

Gonzalez-Franquesa, A. et al. Mass-spectrometry-based proteomics reveals mitochondrial supercomplexome plasticity. Cell Rep. 35, 109180 (2021).

Article  CAS  PubMed  Google Scholar 

Granata, C. et al. High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content. Nat. Commun. 12, 7056 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Frenzel, M., Rommelspacher, H., Sugawa, M. D. & Dencher, N. A. Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex. Exp. Gerontol. 45, 563–572 (2010).

Article  CAS  PubMed  Google Scholar 

Gómez, L. A., Monette, J. S., Chavez, J. D., Maier, C. S. & Hagen, T. M. Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart. Arch. Biochem. Biophys. 490, 30–35 (2009).

Article  PubMed  PubMed Central  Google Scholar 

Lombardi, A. et al. Defining the transcriptomic and proteomic profiles of rat ageing skeletal muscle by the use of a cDNA array, 2D- and Blue native-PAGE approach. J. Proteom. 72, 708–721 (2009).

Article  CAS  Google Scholar 

Lopez-Fabuel, I. et al. Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes. Proc. Natl Acad. Sci. USA 113, 13063–13068 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maranzana, E., Barbero, G., Falasca, A. I., Lenaz, G. & Genova, M. L. Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I. Antioxid. Redox Signal 19, 1469–1480 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cogliati, S. et al. Mechanism of super-assembly of respiratory complexes III and IV. Nature 539, 579–582 (2016).

Article  CAS  PubMed  Google Scholar 

Fernández-Vizarra, E. et al. SILAC-based complexome profiling dissects the structural organization of the human respiratory supercomplexes in SCAFI KO cells. Biochim. Biophys. Acta Bioenerg. 1862, 148414 (2021).

Article  PubMed  Google Scholar 

Calvo, E. et al. Functional role of respiratory supercomplexes in mice: SCAF1 relevance and segmentation of the Qpool. Sci. Adv. 6, eaba7509 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

García‐Poyatos, C. et al. Scaf1 promotes respiratory supercomplexes and metabolic efficiency in zebrafish. EMBO Rep. 21, e50287 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Zong, S. et al. Structure of the intact 14-subunit human cytochrome c oxidase. Cell Res 28, 1026–1034 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fernández-Vizarra, E. et al. Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. 34, 1792–1808.e6 (2022).

Article  PubMed  Google Scholar 

Benegiamo, G. et al. COX7A2L genetic variants determine cardiorespiratory fitness in mice and human. Nat. Metab. 4, 1336–1351 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Althoff, T., Mills, D. J., Popot, J.-L. & Kühlbrandt, W. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J. 30, 4652–4664 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Davies, K. M., Blum, T. B. & Kühlbrandt, W. Conserved in situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants. Proc. Natl Acad. Sci. USA 115, 3024–3029 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nesterov, S. et al. Ordered clusters of the complete oxidative phosphorylation system in cardiac mitochondria. Int. J. Mol. Sci. 22, 1–10 (2021).

Article  Google Scholar 

Letts, J. A. & Sazanov, L. A. Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain. Nat. Struct. Mol. Biol. 24, 800–808 (2017).