Apolipoproteins L1 and L3 control mitochondrial membrane dynamics.

Publication date: Dec 01, 2023

Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking. Like APOL3-KO, APOL1Δ induces PI4KB dissociation from APOL3, linked to reduction of mitophagy flux and production of mitochondrial reactive oxygen species. APOL1 and APOL3, respectively, can interact with the mitophagy receptor prohibitin-2 and the mitophagosome membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). While APOL1 conditions PI4KB and APOL3 involvement in mitochondrion fission and mitophagy, APOL3-VAMP8 interaction promotes fusion between mitophagosomal and endolysosomal membranes. We propose that APOL3 controls mitochondrial membrane dynamics through interactions with the fission factor PI4KB and the fusion factor VAMP8.

Concepts Keywords
Calcium APOL1 risk variants
Endolysosomal COVAN
Iiib COVID-19-associated nephropathy
Kinase CP: Cell biology
Trafficking HIV-associated nephropathy
HIVAN
inflammation
interferon 1
kidney disease
mitochondrion fission/fusion
mitophagy

Semantics

Type Source Name
disease VO report
drug DRUGBANK Calcium
pathway KEGG Autophagy
disease MESH dissociation
pathway KEGG Mitophagy
disease IDO production
disease MESH COVID-19
disease IDO cell
disease MESH HIV-associated nephropathy
disease MESH inflammation
disease MESH kidney disease

Original Article

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