CLPB公司
生物
线粒体膜间隙
膜间隙
细胞生物学
线粒体
蛋白质聚集
德隆
生物化学
细菌外膜
泛素连接酶
泛素
热休克蛋白
基因
大肠杆菌
作者
Megan J. Baker,Karl Blau,Alexander Anderson,Catherine S Palmer,Laura F. Fielden,Jordan J. Crameri,Dusanka Milenkovic,David R. Thorburn,Ann E. Frazier,Thomas Langer,Diana Stojanovski
标识
DOI:10.1083/jcb.202305087
摘要
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 CLPB, HAX1, HTRA2, and the inner membrane quality control proteins (STOML2, PARL, YME1L1; SPY complex), with CLPB deficiency impeding SPY complex function by virtue of protein aggregation in the intermembrane space. We conclude that there is an interdependency of mitochondrial QC components at the intermembrane space/inner membrane interface, and perturbations to this network may underscore CLPB disease pathology.
科研通智能强力驱动
Strongly Powered by AbleSci AI