Publisher Correction: Mitochondrial protein-induced stress triggers a global adaptive transcriptional programme

Mitochondrial protein import clogging as a mechanism of disease

“…CIS1 upregulation is the hallmark of the mitochondrial compromised protein import response (mitoCPR) ( Weidberg and Amon, 2018 ). We also found that RPN4 , HSP82 , SSA3 , and SSA4 are transiently upregulated ( Figure 4—figure supplement 3C–F ), consistent with previously published gene activation patterns induced by a synthetic mitochondrial protein import clogger ( Boos et al, 2019 ). Thus, transcriptional responses further suggest that Aac2p A128P clogs the protein import machinery.…”

“…In addition to defective mitochondrial biogenesis and energy metabolism, it also causes toxic accumulation and aggregation of mitochondrial preproteins in the cytosol, a process termed mitochondrial Precursor Overaccumulation Stress (mPOS) ( Wang and Chen, 2015 ; Coyne and Chen, 2018 ; Song et al, 2021 ). To prevent these consequences, many cellular safeguards have been identified that can maintain protein import efficiency and/or mitigate mPOS ( Backes et al, 2021 ; Weidberg and Amon, 2018 ; Boos et al, 2019 ; Izawa et al, 2012 ; Wrobel et al, 2015 ; Nargund et al, 2015 ; Izawa et al, 2017 ; Hansen et al, 2018 ; Zurita Rendón et al, 2018 ; Liu et al, 2019 ; Mårtensson et al, 2019 ; Su et al, 2019 ; Ordureau et al, 2020 ; Phu et al, 2020 ; Xiao et al, 2021 ; Shakya et al, 2021 ; Xin et al, 2022 ; Sam et al, 2021 ; Schulte et al, 2023 ; Dewar et al, 2022 ; Krämer et al, 2023 ). So far, studies on mitochondrial stressors that impair protein import have been mainly focused on mutations that directly affect the core protein import machinery, synthetic clogger proteins, or on pharmacological interventions that reduce Δψ ( Song et al, 2021 ).…”

Impaired phosphatidylethanolamine metabolism activates a reversible stress response that detects and resolves mutant mitochondrial precursors

“…When grown in dextrose alone, PDR5, which encodes the major drug pump, and the mito-CPR marker CIS1 were the two most upregulated genes in ::LGS versus ::WT ( Figure 7E). Additional genes in the Mitoprotein-Induced Stress Response (Boos et al, 2019;Boos et al, 2020), including RPN4 and PDR3 that function upstream of CIS1, were also significantly upregulated in ::LGS versus ::WT ( Figure S4F). Many of the other top upregulated genes in dextrose-grown ::…”

“…Nearly 99% of the mitochondrial proteome (~1000 proteins in yeast and ~1500 in mammals) is encoded in the nucleus, translated in the cytosol, and imported into one of four mitochondrial compartments-the outer membrane (OM), intermembrane space (IMS), inner membrane (IM), or matrix. Mitochondrial biogenesis is mediated by a series of dedicated import machineries in each compartment and is safeguarded by the collaborative efforts of an emerging network of factors including those that operate in other cellular compartments (Boos et al, 2019;Bykov et al, 2020;Hansen et al, 2018;Martensson et al, 2019;Matsumoto et al, 2019;Shpilka and Haynes, 2018;Wang and Chen, 2015;Weidberg and Amon, 2018;Wrobel et al, 2015). A small proportion of the nuclear-encoded mitochondrial proteome mediates and/or facilitates lipid biosynthetic or trafficking steps critical for the proper functioning of this organelle (Acoba et al, 2020;Sam et al, 2019).…”