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TitleStructural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress.
Journal, issue, pagesSci Adv, Vol. 12, Issue 10, Page eaed3579, Year 2026
Publish dateMar 6, 2026
AuthorsKenneth Ehses / Jorge P López-Alonso / Odetta Antico / Yannik Lang / Till Rudack / Abdussalam Azem / Miratul M K Muqit / Iban Ubarretxena-Belandia / Rubén Fernández-Busnadiego /
PubMed AbstractCells have evolved organelle-specific responses to maintain protein homeostasis (proteostasis). During proteostatic stress, mitochondria down-regulate translation and enhance protein folding, yet the ...Cells have evolved organelle-specific responses to maintain protein homeostasis (proteostasis). During proteostatic stress, mitochondria down-regulate translation and enhance protein folding, yet the underlying mechanisms remain poorly defined. Here, we used cryo-electron tomography to observe the structural consequences of mitochondrial proteostatic stress within human cells. We detected protein aggregates within the mitochondrial matrix, accompanied by a marked remodeling of cristae architecture. Concomitantly, the number of mitochondrial ribosome complexes was significantly reduced. Mitochondrial Hsp60 (mHsp60), a key protein folding machine, underwent major conformational changes to favor complexes with its co-chaperone mHsp10. We visualized the interactions of mHsp60 with native substrate proteins and determined in vitro mHsp60 cryo-electron microscopy structures enabling nucleotide state assignment of the in situ structures. These data converge on a model of the mHsp60 functional cycle and its essential role in mitochondrial proteostasis. More broadly, our findings reveal structural mechanisms governing mitochondrial protein biosynthesis and their remodeling under proteostatic stress.
External linksSci Adv / PubMed:41779846 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution7.76 - 22.89 Å
Structure data

EMDB-55203: Subtomogram average of the 39S mitochondrial ribosome from HeLa
Method: EM (subtomogram averaging) / Resolution: 15.92 Å

EMDB-55204: Subtomogram average of the 55S mitochondrial ribosome from HeLa
Method: EM (subtomogram averaging) / Resolution: 22.89 Å

EMDB-55205: Subtomogram average of the mtHsp60 singlering complex from HeLa
Method: EM (subtomogram averaging) / Resolution: 13.67 Å

EMDB-55206: Subtomogram average of the mtHsp60:mtHsp10 half-football complex from HeLa
Method: EM (subtomogram averaging) / Resolution: 14.3 Å

EMDB-55207: Subtomogram average of the mtHsp60:mtHsp10 Football complex from HeLa
Method: EM (subtomogram averaging) / Resolution: 7.76 Å

Source
  • Homo sapiens (human)

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