Journal article
CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex
MJ Baker, KU Blau, AJ Anderson, CS Palmer, LF Fielden, JJ Crameri, D Milenkovic, DR Thorburn, AE Frazier, T Langer, D Stojanovski
Journal of Cell Biology | Published : 2024
Abstract
CLPB is a mitochondrial intermembrane space AAA+ domain–containing disaggregase. CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia; however, the molecular mechanism underscoring disease and the contribution of CLPB substrates to disease pathology remains unknown. Interactions between CLPB and mitochondrial quality control (QC) factors, including PARL and OPA1, have been reported, hinting at dysregulation of organelle QC in disease. Utilizing proteomic and biochemical approaches, we show a stress-specific aggregation phenotype in a CLPB-null environment and define the CLPB substrate profile. We illustrate an interplay between intermembrane space proteins including..
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Grants
Awarded by State Government of Victoria
Funding Acknowledgements
This research was supported by Medical Research Future Fund Genomics Health Futures Mission-2020 Genomics Health Futures Mission Grant Opportunity (2007959) to D. Stojanovski and D.R. Thorburn; National Health and Medical Research Council Ideas Grant (APP2021085) to D. Stojanovski, D.R.Thorburn, and A.E. Frazier; and Mito Foundation funding (Incubator Grant to D. Stojanovski; Large equipment grant to A.E. Frazier and D.R. Thorburn). T. Langer was supported by grants from the Deutsche Forschungsgemeinschaft (German Research Foundation)-FOR2848 (A01) and the German-Israeli-Project (RA1028/10-2). M.J. Baker, A.J. Anderson, and J.J. Crameri are supported by Australian Government Research Training Program scholarships and by Mito Foundation PhD Top-Up scholarships. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program.