Life Sciences & Biotechnology
Title : | Characterizing Mitochondria-derived Vesicle (MDV) Trafficking through a Proximity Labelling Approach- A possible Novel Mito-nuclear Communication Pathway |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Ananthalakshmy Sundararaman, Rajiv Gandhi Centre for Biotechnology (RGCB), Kerala |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | ananthalakshmys@rgcb.res.in |
Equipments : | Dancing shaker
Deep freezer
pH meter
Type A2 Bio Safety Cabinets
Vaccum pump
Tissue culture water jacketed incubator
Universal Power supply
Vacuum aspiration systems with trap flask |
Details
Executive Summary : | Mitochondria-derived vesicles (MDVs) represent a pathway that operates at the intersection of quality control and vesicular trafficking. MDVs act as a first line of defence against oxidative damage. The damaged or oxidised proteins are targeted for lysosomal degradation through MDVs. The MDVs are cargo selective and a subset of these vesicles are shown to be positive for mitochondrial matrix protein Pyruvate dehydrogenase complex (PDH). Mitochondria, having arisen from ancient alphaproteobacteria, are suggested to have created the immense evolutionary pressure for the elaboration of an endomembrane system in the earliest eukaryotes. It is intriguing that mitochondria-derived vesicles (MDVs), discovered recently, might be one of the first kind of intracellular vesicles encountered in ancestral eukaryotes. Therefore, there is likely to be a great extent of unexplored crosstalk between the mitochondria and other cellular organelles through MDVs. In this project, we propose to unearth a novel, quality control independent role for MDVs in mito-nuclear communication. We hypothesise that MDVs could potentially carry mitochondrial proteins like PDH and its chaperone Hsp70 to the nucleus. A study in 2014 revealed that functional pyruvate dehydrogenase complex in the nucleus provides acetyl CoA for acetylation of histones. Since studies on MDV biogenesis and trafficking has recently demonstrated cargo movement between mitochondria and other organelles like lysosomes and peroxisomes, we hypothesise that the functional PDH complex (10 MDa, 45 nm big) travels in MDVs to coordinate mitochondria and nuclear activities in response to changing cellular milieu. We propose to characterise this novel transit route and its cargoes through mutant biotin ligase, TurboID based proximity labelling approaches to detect proteins co-transiting with PDH from the mitochondria to the nucleus. We will undertake these studies in rat heart cardiomyocytes that are critically dependent on healthy and functional mitochondria. This pathway will help us understand disturbances in homeostatic mito-nuclear communication in cardiovascular diseases. |
Total Budget (INR): | 55,53,570 |
Organizations involved