Researchers Discover New Trigger For Mitophagy

1 month ago

Autophagy is fundamentally nan 'rubbish collection' of our cells. If location are problems successful this process, which is truthful important for our health, diseases specified arsenic Parkinson's tin result. In their latest study, starring compartment biologists astatine nan Max Perutz Labs astatine nan University of Vienna investigated mitophagy - a shape of autophagy - and came to a singular conclusion: nan researchers person described a caller trigger for mitophagy.

This find has led to a reassessment of nan level of factors that trigger autophagy. The recently discovered signalling pathways could besides unfastened up caller therapeutic options. The study has been published successful nan renowned diary Nature Cell Biology.

Autophagy is simply a self-cleaning process of nan compartment and is important for compartment wellness successful nan quality body. A blase molecular surveillance bid identifies suspicious substances - surgery compartment components, clumped proteins aliases moreover pathogens - and initiates their removal. Finally, defective compartment components are surgery down and recycled.

Mitophagy is simply a shape of autophagy successful which mitochondria wrong a compartment are specifically degraded. Dysregulation of mitophagy is peculiarly associated pinch Parkinson's disease. A amended knowing of this process is truthful important for combating Parkinson's.

In a caller study led by postdoctoral interrogator Elias Adriaenssens from Sascha Martens' group astatine nan Max Perutz Labs astatine nan University of Vienna, nan scientists uncover a caller system for triggering mitophagy. Until now, investigation has focused heavy connected nan 'PINK1/Parkin signalling pathway'. Signalling pathways are utilized to transmit accusation wrong cells. These analyzable networks of molecules power captious cellular functions specified arsenic growth, division, compartment decease and, indeed, mitophagy.

"When we looked astatine nan large picture, it became clear that, isolated from nan much-studied 'PINK1/Parkin pathway', location were immense gaps successful our knowledge of different mitophagy pathways. Our laboratory has explored these neglected areas by utilizing biochemical reconstitutions to summation basal mechanistic insights."

Elias Adriaenssens, Study Leader and Postdoctoral Researcher, University of Vienna

Newly discovered pathways are nary exception

"We recovered that NIX and BNIP3 - 2 known mitophagy receptors - tin trigger autophagy without binding to FIP200 (a protein), which was rather unexpected," explains Adriaenssens.

FIP200 is considered basal for triggering autophagy. "This presented america pinch a puzzle. Despite extended testing, we were incapable to observe immoderate relationship betwixt FIP200 and either of nan 2 receptors - which raises nan important mobility of really they usability without this supposedly important component," he adds.

However, wide spectrometry revealed that different autophagy components, known arsenic WIPI proteins, hindrance to these mitochondrial receptors. Since WIPI proteins were antecedently thought to enactment later successful nan signalling pathway, their engagement successful triggering autophagy was surprising. Follow-up experiments confirmed these interactions and suggested that WIPI-mediated recruitment is not an exception, but whitethorn mediate antecedently chartless pathways successful selective autophagy.

"This is an breathtaking find - it reveals a parallel trigger for selective autophagy. Instead of a single, cosmopolitan mechanism, cells look to usage different molecular strategies depending connected nan receptor and context. Until now, nary 1 has considered WIPI proteins to beryllium cardinal players successful triggering autophagosome formation, but our find could alteration that view," explains Adriaenssens.

Potential for caller therapies for Parkinson's disease

Looking ahead, nan study raises an important question: How do cells determine betwixt replacement mitophagy signalling pathways - why do immoderate receptors usage 1 and others nan other, and what factors find which pathway is used? Distinguishing betwixt selective mitophagy signalling pathways could pave nan measurement for therapies that specifically activate 1 pathway to compensate for defects successful nan other, which has semipermanent imaginable for nan curen of Parkinson's disease.

Source:

Journal references:

Adriaenssens, E., et al. (2025). Reconstitution of BNIP3/NIX-mitophagy initiation reveals hierarchical elasticity of nan autophagy machinery. Nature Cell Biology. doi.org/10.1038/s41556-025-01712-y