A new study by the Institute for Research in Biomedicine (IRB), affiliated with Università della Svizzera italiana (USI), reveals how our cells recognise and selectively dispose of their damaged organelles. Published in the prestigious journal Nature Cell Biology, the study titled “The intrinsically disordered regions of organellophagy receptors are interchangeable and control organelle fragmentation, ER-phagy and mitophagy flux” provides new insights into a fundamental mechanism essential for cellular health known as autophagy. This research has significant implications for our understanding and treatment of various diseases.
The cells in our bodies operate through small internal compartments known as organelles, each serving a specific purpose, such as producing energy, eliminating toxins, and synthesising proteins, among others. Similar to the gears of a machine, these organelles can deteriorate or malfunction, particularly as we age or in the presence of disease.
The research conducted by Mikhail Rudinskiy, Carmela Galli, and Andrea Raimondi from the group led by Prof. Maurizio Molinari has shed light on a crucial mechanism that cells use to recognise and selectively dismantle damaged organelles. This study focuses specifically on the endoplasmic reticulum, which is responsible for protein production, and mitochondria, the organelles that provide energy to our cells.
The heart of the discovery is the identification of “disordered regions” (IDRs) present on the membrane proteins of these organelles. These regions act as alarm signals: when they become accessible, they indicate to the cell that part of the organelle is no longer functioning as it should. In response, the cell fragments the damaged organelle and activates its removal via lysosomes, which are cellular “recycling centres”.
This study helps us understand how cells maintain internal balance by eliminating what is no longer needed or could become toxic. It is an important step toward developing therapeutic strategies that help cells defend themselves against damage associated with ageing or disease.
Article:
Mikhail Rudinskiy, Carmela Galli, Andrea Raimondi & Maurizio Molinari
Nature Cell Biology (2025)
