NIPSNAP1 AND NIPSNAP2 RECRUIT AUTOPHAGY RECEPTORS TO FACILITATE MITOPHAGY
By
Yakubu Princely Abudu
Molecular Cancer Research Group
Department of Medical Biology
Mitophagy, the selective clearance of surplus, damaged or dysfunctional mitochondrial by autophagy is an important quality control process required for maintenance of cellular homeostasis and prevention of disease. Although, a lot of work has been devoted to understanding this process, the factors that determine the fate of surplus or damaged mitochondria are not fully understood. We, in collaboration with the group of Anne Simonsen have discovered that the mitochondrial matrix proteins NIPSNAP1 (4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1) and NIPSNAP2, members of an evolutionary conserved protein family, accumulate on the mitochondria surface upon depolarization. Here they recruit proteins involved in selective autophagy, including autophagy receptors and ATG8 proteins, thus functioning as an “eat-me signal” for mitophagy. NIPSNAP1 and NIPSNAP2 function redundantly in mitophagy and are predominantly expressed in different tissues. Zebrafish lacking a functional Nipsnap1 display a Parkinsonian phenotype, including reduced mitophagy in the brain, loss of dopaminergic neurons, reduced motor activity and increased oxidative stress.
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