Life Sciences & Biotechnology
Title : | Investigating novel mitochondrial fission pathways in organelle quality control |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Thomas J Pucadyil, Indian Institute of Science Education and Research (IISER) Pune, Maharashtra |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | pucadyil@iiserpune.ac.in |
Equipments : | Laser free spinning disk confocal |
Details
Executive Summary : | Mitochondria are dynamic double-membraned tubular networks that house respiratory chain complexes, manage biosynthesis of iron-sulfur cluster proteins and lipids, buffer cellular calcium, and affect programmed cell death. Their proper function relies on constant surveillance mechanisms that maintain organelle integrity through elaborate quality control (QC) mechanisms. These mechanisms function locally by removing damaged mitochondrial proteins and globally by sequestering damaged fragments of the entire organelle. Impaired QC mechanisms are linked to aging and various diseases. Pathways involving local proteolysis, processing of mitochondrial proteins via the ubiquitin-proteosome ERAD-like pathway, and autophagic PINK1/PARKIN, NIX/BNIP3 and cardiolipin-mediated mitophagy are relatively well characterized. Recent studies have revealed an alternate QC pathway that involves vesiculation of the organelle to generate mitochondria-derived vesicles (MDVs). MDVs function to deliver specific mitochondrial proteins to the late endosome/multivesicular bodies, and are defined as organelles of 70-150 nm in size. To identify these mechanisms, tissue lysates will bescreened on artificial membrane templates designed to mimic the mitochondrial outer membrane and topologically mimic the putative neck-like intermediates of emergent MDVs. Proteins identified as important for fission will be tested for MDV release in assays involving purified mitochondria tethered on surfaces to become organized as a connected tubular network. The physiological relevance of MDVs to global quality control pathways will be tested in appropriate cellular model systems. |
Total Budget (INR): | 82,68,080 |
Organizations involved