# Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress

## TL;DR

The study reveals how mitochondria restructure their protein-making systems when under stress to maintain protein balance.

## Contribution

The paper provides structural insights into mitochondrial proteostatic stress using cryo–electron tomography and in vitro structures of mHsp60.

## Key findings

- Protein aggregates and cristae remodeling occur in mitochondria under proteostatic stress.
- Mitochondrial ribosome complexes decrease during stress, and mHsp60 undergoes conformational changes.
- Structural data of mHsp60 interactions reveal its functional cycle in mitochondrial protein folding.

## Abstract

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.

Cryo–electron tomography reveals how mitochondria reorganize their translation and folding systems under proteostatic stress.