Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes DOI Open Access

Shigeo MATSUMOTO,

Yoshiki Kogure,

Suzuka Ono

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Yeast Msp1 is a dual-localized AAA-ATPase on the mitochondrial outer membrane (OM) and peroxisomal membrane. We previously showed that transfers mistargeted tail-anchored (TA) proteins from mitochondria to endoplasmic reticulum (ER) for degradation or delivery their original destinations. However, mechanism by which in peroxisomes handles authentic TA remains unclear. show newly synthesized Pex15 targeted primarily via Pex19- Pex3-dependent pathway. Mistargeted OM extracted Msp1, transferred ER guided-entry of pathway Pex19-Pex3 Intriguingly, endogenous localized also membranes but returns These results suggest correct localization relies not only initial targeting constant re-routing Pex19-Pex3.

Language: Английский

Overcoming Fluorescence Loss in mEOS-based AAA+ Unfoldase Reporters Through Covalent Linkage DOI Creative Commons

Isabella R. Walter,

Baylee A. Smith,

Dominic Castanzo

et al.

Protein Expression and Purification, Journal Year: 2025, Volume and Issue: unknown, P. 106724 - 106724

Published: April 1, 2025

Language: Английский

Citations

0
The ATP-driven extractor ATAD1/Msp1 proof-reads protein translocation into mitochondria DOI Creative Commons
Maria Bohnert, Christos Gatsogiannis, Johannes M. Herrmann

et al.

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(9), P. 698 - 699

Published: Aug. 1, 2024

The accumulation of translocation intermediates in the mitochondrial import machinery threatens cellular fitness and is associated with cancer neurodegeneration. A recent study by Weidberg colleagues identifies ATAD1 as an ATP-driven extraction machine on surface that pulls precursors into cytosol to prevent clogging pores.

Language: Английский

Citations

2
Energetic requirements and mechanistic plasticity in Msp1-mediated substrate extraction from lipid bilayers DOI Creative Commons

Baylee A. Smith,

Deepika Gaur,

Nathan Walker

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Abstract AAA+ proteins are essential molecular motors involved in numerous cellular processes, yet their mechanism of action extracting membrane from lipid bilayers remains poorly understood. One roadblock for mechanistic studies is the inability to generate subunit specific mutations within these hexameric proteins. Using mitochondrial protein Msp1 as a model, we created covalently linked dimers with varying combinations wild type and catalytically inactive E193Q mutations. The wide range ATPase rates constructs allows us probe how uses energy ATP hydrolysis perform thermodynamically unfavorable task removing transmembrane helix (TMH) bilayer. Our vitro vivo assays reveal non-linear relationship between extraction, suggesting minimum rate required effective TMH extraction. While structural data often supports sequential clockwise/2-residue step (SC/2R) hydrolysis, our biochemical evidence suggests plasticity coordinates subunits, potentially allowing robustness processing challenging substrates. This study enhances understanding drive mechanical work provides foundational insights about energetic requirements extraction coordination

Language: Английский

Citations

1
The Integrated Stress Response Suppresses PINK1-dependent Mitophagy by Preserving Mitochondrial Import Efficiency DOI
Mingchong Yang,

Zengshuo Mo,

K. J. Walsh

et al.

Published: Oct. 17, 2024

Abstract Mitophagy is crucial for maintaining mitochondrial health, but how its levels adjust to different stress conditions remains unclear. In this study, we investigated the role of DELE1-HRI axis integrated response (ISR) in regulating mitophagy, a key pathway. Our findings show that ISR suppresses mitophagy under non-depolarizing by positively protein import, independent ATF4 activation. Mitochondrial import regulated rate synthesis both depolarizing and stress. Without ISR, increased overwhelms machinery, reducing efficiency. Under stress, heavily impaired even with active leading significant PINK1 accumulation. contrast, allows more efficient presence resulting lower mitophagy. becomes severely compromised, causing accumulation reach threshold necessary trigger These reveal novel link between ISR-regulated synthesis, offering potential therapeutic targets diseases associated dysfunction.

Language: Английский

Citations

0
Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes DOI Open Access

Shigeo MATSUMOTO,

Yoshiki Kogure,

Suzuka Ono

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Yeast Msp1 is a dual-localized AAA-ATPase on the mitochondrial outer membrane (OM) and peroxisomal membrane. We previously showed that transfers mistargeted tail-anchored (TA) proteins from mitochondria to endoplasmic reticulum (ER) for degradation or delivery their original destinations. However, mechanism by which in peroxisomes handles authentic TA remains unclear. show newly synthesized Pex15 targeted primarily via Pex19- Pex3-dependent pathway. Mistargeted OM extracted Msp1, transferred ER guided-entry of pathway Pex19-Pex3 Intriguingly, endogenous localized also membranes but returns These results suggest correct localization relies not only initial targeting constant re-routing Pex19-Pex3.

Language: Английский

Citations

0