Stress adaptation of mitochondrial protein import by OMA1-mediated degradation of DNAJC15
Lara Kroczek, Hendrik Nolte, Yvonne Lasarzewski, Ishita Agrawal, Thibaut Molinié, Daniel Curbelo Piñero, Kathrin Lemke, Elena Rugarli, Thomas Langer
TL;DR
The study shows how mitochondria adapt to stress by degrading a key protein, DNAJC15, which affects protein import and causes stress responses in other parts of the cell.
Contribution
The paper reveals a new mechanism by which OMA1 and AFG3L2 regulate mitochondrial protein import during stress.
Findings
OMA1 cleaves DNAJC15, leading to its degradation by AFG3L2.
Loss of DNAJC15 impairs mitochondrial protein import and OXPHOS biogenesis.
Accumulation of non-imported proteins triggers an unfolded protein response in the endoplasmic reticulum.
Abstract
Mitochondria dynamically adapt to cellular stress to ensure cell survival. The stress-regulated mitochondrial peptidase OMA1 orchestrates these adaptive responses, which limit mitochondrial fusion and promote mitochondrial stress signaling and metabolic rewiring. Here, we show that cellular stress adaptation involves OMA1-mediated regulation of mitochondrial protein import and OXPHOS biogenesis. OMA1 cleaves the mitochondrial chaperone DNAJC15 and promotes its degradation by the m-AAA protease AFG3L2. Loss of DNAJC15 impairs mitochondrial protein import and restricts OXPHOS biogenesis under conditions of mitochondrial dysfunction. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum, inducing an unfolded protein response. Our results demonstrate stress-dependent changes in mitochondrial protein import as part of the OMA1-mediated mitochondrial stress response…
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Taxonomy
TopicsMitochondrial Function and Pathology · GDF15 and Related Biomarkers · Adipose Tissue and Metabolism