Biology subjects

Mamriev, D.

Publications and source records attributed to Mamriev, D..

2 recordsLinked to original sources

bioRxiv2026

Rapid optogenetic manipulation of autophagy reveals that the nuclear pore complex is a robust autophagy substrate

Autophagy, a conserved recycling process, manages intracellular quality control to mitigate stress. To determine the rapid effects of autophagy perturbation, we developed the first optogenetic tool to rapidly inhibit autophagy, termed ASAP. Our approach leverages light-induced proteolytic cleavage to selectively inhibit autophagy within 5 minutes of light exposure, providing a precise and dynamic approach to study autophagy regulation. Proteomic profiling with ASAP revealed the most tightly regulated autophagy substrates along with novel, previously unidentified substrates, including nuclear pore complex (NPC) proteins. Interestingly, autophagy regulates quality control of cytoplasmic complexes of nucleoporins via specific LC3-interacting regions (LIRs), sparing nuclear pore complex proteins embedded in the nuclear envelope. Upon rapid autophagy inhibition, incomplete nucleoporin complexes accumulate and instead of undergoing autophagic degradation, cytoplasmic nucleoporin complexes aggregate in processing bodies (P bodies). Using ASAP, we demonstrate rapid and specific inhibition of autophagy, revealing that nuclear pore complex proteins are tightly regulated autophagy substrates.

cell biology↗

bioRxiv2025

CED-3 caspase promotes dismantling but not onset of non-apoptotic linker cell death in C. elegans

Nuclear degradation accompanies cell death. To study this process, we followed nuclear dismantling of the C. elegans linker cell, which undergoes non-apoptotic morphologically-conserved cell death characterized by nuclear envelope crenellations and cell splitting. We show that although linker cell death is cell autonomous, nucleus elimination follows engulfment and is blocked in rab-35 and arf-6 phagosome maturation mutants. Surprisingly, although linker cell death is independent of the apoptotic caspase CED-3, CED-3 is partially required within the linker cell, and upstream of RAB-35 and ARF-6, for cell splitting, engulfment, and nucleus elimination. In parallel studies, we found that the kinase inhibitor staurosporine causes mouse embryonic fibroblasts to undergo caspase-independent non-apoptotic death accompanied by nuclear crenellations and, paradoxically, by Caspase-3/7 activation. Our findings suggest mechanistic similarities between staurosporine-induced and linker cell death, revealing that, in some contexts, caspases do not initiate cell death but instead promote subcellular tasks required for cell clearance.

cell biology↗