Targeting and Insertion of Membrane Proteins in Mitochondria

Eaglesfield, Ross; Tokatlidis, Kostas

doi:10.3389/fcell.2021.803205

Cited by 22 publications

(15 citation statements)

References 159 publications

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“…1C), as already reported for other SARS-CoV-2 accessory proteins, such as ORF9b (Jiang et al, 2020). This latter was previously shown to directly interact with the outer mitochondrial membrane protein TOM70 (translocase of outer membrane 70) (Jiang et al, 2020), which forms the translocon complex with other TOM proteins (Eaglesfield & Tokatlidis, 2021). We found that hORF3c and bORF3c proteins colocalize with TOM70 and TOM20 (Suppl Fig.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress and autophagic flow

Mozzi

Oldani

Forcella

et al. 2022

Preprint

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Coronaviruses encode a variable number of accessory proteins that play a role in host-virus interactions, in the suppression of immune responses, or in immune evasion. Accessory proteins in SARS-CoV-2 consist of at least twelve viral proteins whose roles during infection have been extensively studied. Nevertheless, the role of the ORF3c accessory protein, an alternative open reading frame of ORF3a, has remained elusive. Herein, we characterized ORF3c in terms of cellular localization, host's antiviral response modulation, and effects on mitochondrial metabolism. We show that ORF3c has a mitochondrial localization and alters mitochondrial metabolism, resulting in increased ROS production, block of the autophagic flux, and accumulation of autophagosomes/autolysosomes. Notably, we also found that ORF3c induces a shift from glucose to fatty acids oxidation and enhanced oxidative phosphorylation. This is similar to the condition observed in the chronic degenerative phase of COVID-19. Altogether these data suggest that ORF3c could be a key protein for SARS-CoV-2 pathogenesis and that it may play a role in disease progression.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress and autophagic flow

Mozzi

Oldani

Forcella

et al. 2022

Preprint

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“…Therefore, it indicates that these proteins should be located on the mitochondrial membrane. Furthermore, these proteins carry MT peptide of ATP synthase δ subunit, which is a transmembrane protein in the mitochondrial inner membrane, so they should be led to the mitochondrial inner membrane via the TOM-TIM pathway [ 74 , 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the Yeast Saccharomyces cerevisiae

Tsai

Hsieh

Hsu

et al. 2022

IJMS

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Mitochondrial respiratory complex I catalyzes electron transfer from NADH to ubiquinone and pumps protons from the matrix into the intermembrane space. In particular, the complex I subunits Nad1, Nad2, Nad4, and Nad5, which are encoded by the nad1, nad2, nad4, and nad5 genes, reside at the mitochondrial inner membrane and possibly function as proton (H+) and ion translocators. To understand the individual functional roles of the Nad1, Nad2, Nad4, and Nad5 subunits in bamboo, each cDNA of these four genes was cloned into the pYES2 vector and expressed in the mitochondria of the yeast Saccharomyces cerevisiae. The mitochondrial targeting peptide mt gene (encoding MT) and the egfp marker gene (encoding enhanced green fluorescent protein, EGFP) were fused at the 5′-terminal and 3′-terminal ends, respectively. The constructed plasmids were then transformed into yeast. RNA transcripts and fusion protein expression were observed in the yeast transformants. Mitochondrial localizations of the MT-Nad1-EGFP, MT-Nad2-EGFP, MT-Nad4-EGFP, and MT-Nad5-EGFP fusion proteins were confirmed by fluorescence microscopy. The ectopically expressed bamboo subunits Nad1, Nad2, Nad4, and Nad5 may function in ion translocation, which was confirmed by growth phenotype assays with the addition of different concentrations of K+, Na+, or H+.

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“…[29] However, it has been proposed that some tail-anchored and polytopic proteins are inserted into the OM in a spontaneous, lipid-assisted manner which needs further investigation. [30,31] The small Τims are a family of essential proteins of the intermembrane space, which bear twin CX3C motifs, and together with other cysteine-rich proteins, utilize the Mitochondrial Intermembrane space import and Assembly machinery (MIA) redox-based machinery to be properly targeted. This system consists of the oxidoreductase Mia40 which works together with the sulfhydryl oxidase essential for respiration and vegetative growth Erv1 (Augmenter of Liver Regeneration -ALR in mammals) to introduce intramolecular disulfide bonds in their substrate precursors.…”

Section: Overview Of the Yeast Mitochondrial Protein Import Systemmentioning

confidence: 99%

Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond

2023

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Mitochondria hold diverse and pivotal roles in fundamental processes that govern cell survival, differentiation, and death, in addition to organismal growth, maintenance, and aging. The mitochondrial protein import system is a major contributor to mitochondrial biogenesis and lies at the crossroads between mitochondrial and cellular homeostasis. Recent findings highlight the mitochondrial protein import system as a signaling hub, receiving inputs from other cellular compartments and adjusting its function accordingly. Impairment of protein import, in a physiological, or disease context, elicits adaptive responses inside and outside mitochondria. In this review, we discuss recent developments, relevant to the mechanisms of mitochondrial protein import regulation, with a particular focus on quality control, proteostatic and metabolic cellular responses, triggered upon impairment of mitochondrial protein import. K E Y W O R D Smetabolism, mitochondrial protein import, mitochondrial unfolded protein response, mitophagy, proteostasis Recent findings from system biology studies in whole cells (in vivo) have highlighted the mitochondrial protein import system as a critical

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Targeting and Insertion of Membrane Proteins in Mitochondria

Cited by 22 publications

References 159 publications

SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress and autophagic flow

SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress and autophagic flow

Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the Yeast Saccharomyces cerevisiae

Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond

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