Julian M Carosi

2 months ago | nature.com | Julian M Carosi |Sharad Kumar |Ruchi Umargamwala |Shannon Nicolson |Donna Denton |Jantina Manning

Autophagy-dependent cell death (ADCD) is a context-specific form of programmed cell death that plays an important role in development and homeostasis. During Drosophila metamorphosis, hormonal cues modulate growth and other signalling cascades which results in autophagy-dependent degradation of the obsolete larval midgut. While this process does not require caspase activity or apoptotic machinery, several canonical autophagy-related proteins are also dispensable, suggesting additional regulators may be involved in effectively eliminating the larval midgut. Ubiquitination, a process that attaches one or more ubiquitin moieties to a substrate through sequential reactions involving a cascade of enzymes, plays a critical role in autophagy. As the specific role(s) of ubiquitination in ADCD has not been explored, we previously performed a RNAi-mediated knockdown screen of over 250 ubiquitin machinery genes in GFP-labelled Drosophila larval midguts and identified 18 candidate regulators of midgut degradation. In this work, we screened candidate genes for a role in autophagy-dependent midgut degradation by analysing mosaic clones and genetic interactions with Atg1. Validation and further studies into the ubiquitin conjugating enzyme, Effete (Eff), and two ubiquitin ligases, Cullin-4 (Cul4) and Supernumerary limbs (Slmb), demonstrated interplay between ubiquitination and the autophagy machinery in coordinating autophagy-dependent midgut degradation.

Dec 9, 2024 | biorxiv.org | Linh Dang |Alexis Martin |Julian M Carosi |Jemima R Gore

AbstractAutophagy is a naturally conserved mechanism crucial for degrading and recycling damaged organelles and proteins to support cell survival. This process slows biological ageing and age-related disease in preclinical models. However, there has been little translation of autophagy to the clinic, and we have identified a lack of measurement tools for physiological human autophagy as a barrier.

Sep 11, 2024 | biorxiv.org | Alexis Martin |Sofia Hassiotis |Julian M Carosi |Leanne K Hein

AbstractAutophagy is a waste-disposal pathway that protects against age-related pathology. It is widely accepted that autophagy declines with age, yet role that sex and diet-related obesity play during aging remain unknown. Here, we present the most comprehensive in vivo study of autophagic flux to date.