The RBG-1-RBG-2 complex modulates autophagy activity by regulating lysosomal biogenesis and function in C. elegans

Area of Science:

• Cell Biology
• Genetics
• Molecular Biology

Background:

• Vici syndrome is a severe multisystem disorder linked to EPG5 gene mutations.
• EPG5 deficiency impairs autophagy, leading to autolysosome accumulation, but the mechanism is unclear.

Purpose of the Study:

• To investigate the mechanism of autophagy defect in EPG5 loss-of-function.
• To identify factors regulating lysosomal function in Vici syndrome pathogenesis.

Main Methods:

• Utilized C. elegans models with mutations in epg-5 and rbg-1.
• Assessed autophagy, lysosomal biogenesis, and RAB-7 mobility.
• Investigated the role of the RBG-1-RBG-2 complex and RAB-7 dynamics.

Main Results:

• Loss of RBG-1-RBG-2 complex function ameliorated autophagy defects in epg-5 mutants.
• rbg-1 loss promoted lysosomal biogenesis and function, suppressing autolysosome accumulation.
• RBG-1-RBG-2 complex modulates RAB-7 dynamics, impacting lysosomal function and Vici syndrome pathology.

Conclusions:

• The RBG-1-RBG-2 complex regulates lysosomal biogenesis through RAB-7 dynamics.
• Targeting this complex offers a potential therapeutic strategy for Vici syndrome.