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MRC Mitochondrial Biology Unit

 

Dr Julien Prudent

MRC Investigator

 

 

 

 

Mitochondrial cell biology: Understanding the molecular mechanisms and functions of mitochondrial dynamics and membrane contact sites

Beyond their role in energy production, the concept of mitochondria as a signalling organelle has emerged, with mitochondria being implicated in processes critical for the survival and homeostatic adaptation of the cell, including cell death, calcium homeostasis, redox status, inflammation and immunity. Mitochondria have a characteristic architecture composed of a double-membrane structure, with an outer and inner mitochondrial membrane, both of which are constantly remodelled to adapt to the metabolic state of the cell. Mitochondria are dynamic organelles forming an interconnected network which is regulated by cycles of fission and fusion events, in a process known as mitochondrial dynamics. These dynamic shape transitions are not only required to ensure mitochondrial function but also to respond to cellular needs and to control cell fate decisions. Mitochondria also form an elaborate network of organelle interactions by forming mitochondria-organelle contact sites (MOCS) with the endoplasmic reticulum (ER), peroxisomes, endosomes, lysosomes, and lipid droplets. These membranes contact sites are signalling platforms enriched with specific proteins, allowing mitochondria to communicate with other organelles by exchanging signals, metabolites, calcium and lipids. They are critical in regulating mitochondrial architecture and in the execution of multiple cellular functions. However, the functional interplay between mitochondrial dynamics and membrane contact sites are not fully understood. Defects in mitochondrial morphology or MOCS have been associated to human diseases including cancer, diabetes, obesity, metabolic and neurodegenerative diseases, raising the importance of elucidating how mitochondrial dynamics and membrane contact sites control cell fate decisions and how they are involved in health and disease.

Our research group aims 1) to understand the mechanisms regulating mitochondrial dynamics and remodelling and how they govern cell fate decisions, 2) to identify and functionally characterise new proteins regulating mitochondria-organelle contact sites, and 3) to elucidate how mitochondrial membranes remodelling controls mtDNA dynamics, including the mechanisms involved in mtDNA release. We investigate the relevance of these pathways in cell death and survival, cellular metabolism, inflammation as well as to human diseases including cancer. To achieve our scientific goals, we employ cutting-edge microscopy, including confocal and transmission electron microscopy as well as super-resolution live-cell microscopy, coupled to proteomics and analytical biochemical techniques.

PhD Studentship available - starting in January 2022

Biography

Julien Prudent obtained a Master’s degree in Biochemistry (2007) and a Ph.D. in Cell Biology (2011) from the University Claude Bernard Lyon I (Lyon, France). During his Ph.D in the Professor Germain Gillet’s lab, he was investigating the roles of Bcl-2 proteins in calcium signalling during zebrafish embryonic development. He moved to Professor Heidi McBride’s lab at McGill University (Montreal, Canada) as postdoctoral fellow in 2013 to study the interplay between mitochondrial dynamics, membrane contacts sites and cellular homeostasis. He established his independent research group at the MRC Mitochondrial Biology Unit, University of Cambridge (Cambridge, UK), as tenure-track programme leader, in 2016.

Publications

Selected Publications

Xue Y*, Morris JL*, Yang K*, Fu Z, Zhu X, Johnson F, Meehan B, Witowski L, Yasmeen A, Golenar T, Coatham M, Morin G, Monast A, Pilon V, Fiset PO, Jung S, Gonzalez AV, Camilleri-Broet S, Fu L, Postovit L-M, Spicer J, Gotleib WH, Guiot M-C, Rak J, Park M, Lockwood W, Foulkes WD, Prudent J+ & Huang S+ (2021)
SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca 2+ flux to mitochondria
Nat Commun 12, 5404. doi:10.1038/s41467-021-25260-9 *co-first author, +co-corresponding author

Tábara LC, Morris JL & Prudent, J (2021)
The complex dance of organelles during mitochondrial division.
Trends Cell Biol 31, 241-253. doi:10.1016/j.tcb.2020.12.005

Pezet MG, Gomez-Duran A, Klimm F, Aryaman J, Burr SP, Wei, W, Saitou M, Prudent J & Chinnery PF (2021)
Oxygen tension modulates the mitochondrial genetic bottleneck and influences the segregation of a heteroplasmic mtDNA variant in vitro.
Commun. Biol. 4, 584. doi:10.1038/s42003-021-02069-2

Nagashima S, Tábara L-C, Tilokani L, Paupe V, Anand H, Pogson JH, Zunino R, McBride HM & Prudent J (2020)
Golgi-derived PI (4) P-containing vesicles drive late steps of mitochondrial division.
Science 367, 1366-1371. doi:10.1126/science/aax6089

Morita M*, Prudent J*, Basu K, Goyon V, Katsumura S, Hulea L, Pearl D, Siddiqui N, Strack S, McGuirk S, St-Pierre J, Larsson O, Topisirovic I, Vali H, McBride HM, Bergeron JJ & Sonenberg N (2017)
mTOR controls mitochondrial dynamics and cell survival via MTFP1.
Mol Cell 67, 922-935.e5 doi:10.1016/j.molcel.2017.08.013 *equal contribution

Publication profile - Google Scholar

PubMed (last 10 years)

Group Members

Research support
   Mark Johnson
Post-docs
   Roy Chowdhury
   Goncalo de Castro Pereira
   Vincent Paupe
   Luis-Carlos Tabara Rodriguez
   Lisa Tilokani
Post-graduate students
   Jordan Morris
   Mayuko Segawa
   Filipa Santos Viegas

Contacts

Email

Tel: +44(0)1223 252770