Preprint Highlight: ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA- dependent STING signaling

Loss-of-function mutations in VPS13C cause familial Parkinson’s disease (PD) and increase the risk to develop the sporadic form of the disease. However, the underlying disease mechanisms remain unclear. It has been previously established that VPS13C tethers lysosomes with the endoplasmic reticulum (ER) and promotes lipid interchange between both organelles. This study provides a cellular role of VPS13C, specifically regulating the cGAS/STING pathway and contributing to the innate immune response. The authors generate VPS13C knockout HeLa cells and use confocal microscopy and biochemical approaches to show loss of VPS13C leads to altered lysosome lipid composition and mitochondrial DNA leakage. Understanding how VPS13C preserves cellular homeostasis is an exciting discovery for scientists working on neurodegeneration and for cell biologists interested in lysosome-to-mitochondria cross-talk.

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