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<p>The mitochondrial respiratory chain (MRC) complexes, crucial for aerobic energy transduction in eukaryotes, form conserved higher-order structures called supercomplexes (SCs). The elucidation of SC physiological relevance is critical for our understanding of mitochondrial function and bioenergetics but has been hindered by the limited availability of experimental models isolating SC formation as the sole variable. In baker’s yeast, SCs comprise III<sub>2</sub>IV<sub>1</sub> and III<sub>2</sub>IV<sub>2</sub> configurations, which enhance respiratory rates by facilitating cytochrome <i>c</i> diffusion along the SC surface. However, the roles of distinct SC conformations and MRC plasticity remain unclear. To address these questions, we engineered a yeast strain expressing a covalently-linked III<sub>2</sub>IV<sub>2</sub> SC, structurally like the wild-type. Expression of this tethered SC supports robust respiratory activity but selectively impacts cytosolic NADH-driven respiration, due to distinct interactions with the NADH dehydrogenase Nde1. We propose that in yeast mitochondria, substrate-specific respirasome-like SCs contribute to the optimization of electron fluxes and support metabolic flexibility.</p>

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Mitochondrial respirasome-like supercomplexes support metabolic flexibility in yeast

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Mazzen H. Eldeeb,
  • Zoe Cosner,
  • Andreas Carlström,
  • Jeffri-Noelle Mays,
  • Gabriella F. Rodriguez,
  • Jens Berndtsson,
  • Martin Ott,
  • Flavia Fontanesi

摘要

The mitochondrial respiratory chain (MRC) complexes, crucial for aerobic energy transduction in eukaryotes, form conserved higher-order structures called supercomplexes (SCs). The elucidation of SC physiological relevance is critical for our understanding of mitochondrial function and bioenergetics but has been hindered by the limited availability of experimental models isolating SC formation as the sole variable. In baker’s yeast, SCs comprise III2IV1 and III2IV2 configurations, which enhance respiratory rates by facilitating cytochrome c diffusion along the SC surface. However, the roles of distinct SC conformations and MRC plasticity remain unclear. To address these questions, we engineered a yeast strain expressing a covalently-linked III2IV2 SC, structurally like the wild-type. Expression of this tethered SC supports robust respiratory activity but selectively impacts cytosolic NADH-driven respiration, due to distinct interactions with the NADH dehydrogenase Nde1. We propose that in yeast mitochondria, substrate-specific respirasome-like SCs contribute to the optimization of electron fluxes and support metabolic flexibility.