Nanoscale remodeling of mitochondrial architecture duringmtRNA surveillance failure

Abstract

Mitochondria within a cell exhibit heterogeneity in their composition and metabolic functions, and how this specialization shapes the responses of individual organelles to stress is unclear. We applied fluorescence microscopy and in situ cryo-electron tomography to examine the composition of mitochondrial stress bodies and their relationship to inner mitochondrial membrane architecture in the context of a mitochondrial genome expression defect. We discovered that defective mitochondrial RNA processing prompted a loss of inner membrane domain identity, leading to the mislocalization of ATP synthase from cristae edges to the boundary membrane, perturbed cristae morphometrics, and complete cristae loss in a subset of organelles. Mitochondrial stress bodies were enriched with nucleic acid and protein components linked to oxidative pathways, while separate and distinct mitochondrial domains became enriched with oligomerized P5CS, a marker of reductive proline synthesis. We found that consolidation of mitochondrial RNA into stress bodies, as well as ATP synthase remodeling, were regulated independently from P5CS concentration into a subset of the mitochondria. We propose that stress compartmentalization enables independent tuning of the quality control of oxidative pathway components via spatial sequestration from the rest of the mitochondrial network.