Scilight Press

Lysosomal membrane integrity is essential for cellular homeostasis, yet how lysosomes are repaired during metabolic stress remains incompletely understood. In our recent study, we found that lysosomal uptake of lipid droplets during glucose starvation induced lysosomal membrane damage and identified TECPR1 as a key mediator of lysosomal membrane repair. TECPR1 was recruited to compromised lysosomes by binding PI4P on damaged membranes and subsequently engaged KIF1A to drive lysosome-derived membrane tubulation. This tubulation facilitated the removal of damaged membrane components and promoted lysosomal recovery. Functionally, TECPR1-dependent repair maintained lipid metabolic homeostasis and supported cell survival under energy stress. In vivo, TECPR1 deficiency aggravated starvation-induced liver injury in a high-fat diet-induced MAFLD model. In this U&A Point, we discuss this TECPR1-mediated, tubulation-based lysosomal repair pathway and its mechanistic distinction from canonical autophagy and CASM.