Mitochondrial protein import stress and signaling

Samluk, Łukasz; Chrościcki, Piotr; Chacińska, Agnieszka

doi:10.1016/j.cophys.2018.02.010

Cited by 17 publications

(21 citation statements)

References 71 publications

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“…One possible explanation for this difference is that acute mitochondrial stress induces a rapid reaction, in which the mTOR pathway and cap-dependent translation are inhibited. With prolonged mitochondrial stress, in contrast, this beneficial response is lost (D’Amico et al , 2017; Samluk et al , 2018). Although the mechanism of protein synthesis inhibition under long-term mitochondrial stress is not completely clear, we proposed a model in which long-term mitochondrial stress triggers adaptive responses for protection against excessive inhibition of protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress

Samluk

Urbańska

Kisielewska

et al. 2019

MBoC

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Previous studies demonstrated that cells inhibit protein synthesis as a compensatory mechanism for mitochondrial dysfunction. Protein synthesis can be attenuated by 1) the inhibition of mTOR kinase, which results in a decrease in the phosphorylation of S6K1 and 4E-BP1 proteins, and 2) an increase in the phosphorylation of eIF2α protein. The present study investigated both of these pathways under conditions of short-term acute and long-term mitochondrial stress. Short-term responses were triggered in mammalian cells by treatment with menadione, antimycin A, or CCCP. Long-term mitochondrial stress was induced by prolonged treatment with menadione or rotenone and expression of genetic alterations, such as knocking down the MIA40 oxidoreductase or knocking out NDUFA11 protein. Short-term menadione, antimycin A, or CCCP cell treatment led to the inhibition of protein synthesis, accompanied by a decrease in mTOR kinase activity, an increase in the phosphorylation of eIF2α (Ser51), and an increase in the level of ATF4 transcription factor. Conversely, long-term stress led to a decrease in eIF2α (Ser51) phosphorylation and ATF4 expression and to an increase in S6K1 (Thr389) phosphorylation. Thus, under long-term mitochondrial stress, cells trigger long-lasting adaptive responses for protection against excessive inhibition of protein synthesis.

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Section: Discussionmentioning

confidence: 99%

Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress

Samluk

Urbańska

Kisielewska

et al. 2019

MBoC

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“…An additional cellular strategy to avoid UPS overload under prolonged mitochondrial stress conditions is based on suppression of protein translation both inside and outside of the organelle (Münch, 2018;Samluk et al, 2018;Shpilka and Haynes, 2018). The predominant mechanism of cytosolic translation inhibition is mediated by phosphorylation of the eukaryotic transition initiation factor 2 alpha (eiF2α), which prevents formation of the translation initiation complex (Sonenberg and Hinnebusch, 2009).…”

Section: Mitochondrial Stress Response Mechanismsmentioning

confidence: 99%

Mitochondrial Quality Control Governed by Ubiquitin

Ravanelli

Brave

Hoppe

2020

Front. Cell Dev. Biol.

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Mitochondria are essential organelles important for energy production, proliferation, and cell death. Biogenesis, homeostasis, and degradation of this organelle are tightly controlled to match cellular needs and counteract chronic stress conditions. Despite providing their own DNA, the vast majority of mitochondrial proteins are encoded in the nucleus, synthesized by cytosolic ribosomes, and subsequently imported into different mitochondrial compartments. The integrity of the mitochondrial proteome is permanently challenged by defects in folding, transport, and turnover of mitochondrial proteins. Therefore, damaged proteins are constantly sequestered from the outer mitochondrial membrane and targeted for proteasomal degradation in the cytosol via mitochondrial-associated degradation (MAD). Recent studies identified specialized quality control mechanisms important to decrease mislocalized proteins, which affect the mitochondrial import machinery. Interestingly, central factors of these ubiquitindependent pathways are shared with the ER-associated degradation (ERAD) machinery, indicating close collaboration between both tubular organelles. Here, we summarize recently described cellular stress response mechanisms, which are triggered by defects in mitochondrial protein import and quality control. Moreover, we discuss how ubiquitindependent degradation is integrated with cytosolic stress responses, particularly focused on the crosstalk between MAD and ERAD.

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“…In the nematode Caenorhabditis elegans, an elegant mechanism has been identified demonstrating how mitochondrial damage induces the mitochondrial UPR (UPR mt ) (Nargund et al 2012;Higuchi-Sanabria et al 2018;Samluk et al 2018;Shpilka and Haynes 2018). The cellular localization of the transcription factor ATFS-1 is pivotal for the induction of the UPR mt .…”

Section: Role Of Protein Import In Mitochondrial Stress Responsesmentioning

confidence: 99%

“…6; Nargund et al 2015). In mammals, the three transcription factors ATFS-4, ATFS-5, and CHOP are involved in the induction of the UPR mt by an unknown mechanism (Higuchi-Sanabria et al 2018;Samluk et al 2018;Shpilka and Haynes 2018). Expression of human ATFS-5 can compensate for the loss of ATFS-1 in worms, indicating that basic mechanisms to induce the UPR mt are conserved between worms and humans (Fiorese et al 2016).…”

Section: Role Of Protein Import In Mitochondrial Stress Responsesmentioning

confidence: 99%

Pathways to balance mitochondrial translation and protein import

Priesnitz

Becker

2018

Genes Dev.

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Cytochrome bc 1 complex COB Cbs1 Acts on the 5 ′ untranslated region (UTR) of COB mRNA Associates with mitoribosomes Cbs2 Acts on the 5 ′ UTR of COB mRNA Associates with mitoribosomes Cbp1 Acts on the 5 ′ UTR of COB mRNA Stabilizes COB mRNA Cbp3 Forms a complex with Cpb6 Cbp6 Associates with mitoribosomes Couples translation of COB mRNA with assembly of the cytochrome bc 1 complex Cytochrome c oxidase COX1 Mss51 Acts on the 5 ′ UTR of COX1 mRNA Couples translation of COX1 mRNA with assembly of cytochrome c oxidase Pet309 Binds to COX1 mRNA Stabilizes COX1 mRNA Mam33 Translational activator during fermentative growth Unknown molecular function COX2 Pet111 Acts on the 5 ′ UTR of COX2 mRNA COX3 Pet54 Pet54/Pet122/Pet494 form a complex Pet122 Acts on the 5 ′ UTR of COX3 mRNA Pet494 ATP synthase ATP6 Atp22 Unknown function ATP6/ATP8 Smt1 Translational repressor Binds ATP6/ATP8 mRNA ATP9 Aep1 Unknown function Aep2 Acts on 5 ′ UTR of ATP9 mRNA Atp25 Stabilization of ATP9 mRNA Promotes assembly of Atp9 ring Mitoribosome VAR1 Sov1 Unknown function Protein-encoding mitochondrial genes and their translational regulators in S. cerevisiae are listed. Smt1 acts as translational repressor, while all other translation regulators activate the expression of their target genes.

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Mitochondrial protein import stress and signaling

Cited by 17 publications

References 71 publications

Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress

Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress

Mitochondrial Quality Control Governed by Ubiquitin

Pathways to balance mitochondrial translation and protein import

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