Ribosome-associated chaperones integrate co-translational mitochondrial protein import, stress signaling and proteostasis in Saccharomyces cerevisiae

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ID: 323183
2026
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Abstract
Mitochondrial biogenesis requires the coordinated synthesis, targeting, and import of nuclear-encoded mitochondrial precursor proteins. Although ribosome-associated chaperones support co-translational protein folding, their genetic contributions to mitochondrial protein import and cellular homeostasis remain incompletely defined. Here, we investigate the roles of the nascent polypeptide-associated complex (NAC) and the ribosome-associated Hsp70 system Ssb1/2 in Saccharomyces cerevisiae. We show that NAC and Ssb1/2 have distinct yet partially overlapping functions in the handling of mitochondrial precursor proteins. Loss of NAC activates the mitochondrial retrograde pathway and enhances growth on ethanol as a non-fermentable carbon source without compromising respiratory competence, indicating metabolic adaptation rather than overt mitochondrial dysfunction. In contrast, Ssb1/2 deficiency disrupts cytosolic proteostasis, sensitizes cells to TORC1 inhibition, and impairs autophagy and mitophagy. Using a TEV protease-based import reporter, we show that Ssb1/2 promotes efficient co-translational distribution of precursor proteins, whereas NAC limits the accumulation of misfolded proteins at the mitochondrial surface. Biochemical analyses further reveal that Ssb1/2 supports the association of translating cytosolic ribosomes with the mitochondrial outer membrane, while NAC loss partially restores this interaction in the absence of Ssb1/2. Together, these findings establish NAC and Ssb1/2 as key components of an integrated network linking co-translational targeting, mitochondrial signaling, and cellular homeostasis.
Reference Key
openalex_W7172142194 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors
Journal current genetics
Year 2026
DOI
10.1093/genetics/iyag200
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