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Figure 2. (A) Schematic representation of the membrane contact sites between mitochondria and all other cellular organelles, as well as with the plasma membrane and nucleus. (B) Representative N-Structured Illumination Microscopy (N-SIM) super-resolution image showing membrane contact sites between mitochondria and the endoplasmic reticulum (ER) in Cos-7 cells. Mitochondria and ER were labelled using anti-TOM20 and anti-KDEL antibodies, respectively. Scale bar: 2 um.

Mitochondria do not function in isolation but establish direct contact and communicate with other cellular organelles to exchange metabolites and signals converging on, or streaming from, mitochondria. Mitochondria form an elaborate network of organelle interactions by forming mitochondria-organelle contact sites (MOCS) not only with the endoplasmic reticulum (ER)[1], but also with almost all of organelles of the cell [2] (Figure 2A). These membranes contact sites are signalling platforms enriched in specific proteins, which allow mitochondria to communicate with other organelles by exchanging signals, metabolites, calcium and lipids, and they are critical to regulate mitochondrial homeostasis and to execute multiple cellular functions [3],[4]. While the mitochondria-ER contacts have been extensively studied, how and why mitochondria establish membrane contact sites with other organelles, but also the regulatory mechanisms associated with these signalling platforms are still not well understood.

Our goal is to characterise MOCS by identifying new proteins and pathways involved in their modulation, and to investigate how they converge and govern a multitude of cellular functions. To address these questions, we use confocal, super-resolution and transmission electron microscopy (Figure 2B) coupled with live-cell imaging from genetically manipulated mammalian cells. We combine these methods not only with proteomic and biochemical methods, but also by analysing calcium and lipid fluxes between organelles. Our aim is to investigate the relevance of MOCS during/on cell death and survival events, cellular metabolism and their contribution in the emergence and development of pathological conditions including cancer and neurodegenerative diseases [5],[6].


REFERENCES

  1. Phillips, M. J. & Voeltz, G. K. (2016)
    Structure and function of ER membrane contact sites with other organelles
    Nat Rev Mol Cell Biol 17, 69-82. doi:10.1038/nrm.2015.8
  2. Valm, A. M. et al. (2017)
    Applying systems-level spectral imaging and analysis to reveal the organelle interactome
    Nature 546, 162-167. doi:10.1038/nature22369
  3. Giacomello, M., Pyakurel, A., Glytsou, C. & Scorrano, L. (2020)
    The cell biology of mitochondrial membrane dynamics
    Nat Rev Mol Cell Biol 21, 204-224. doi:10.1038/s41580-020-0210-7
  4. Prudent, J. & McBride, H. M. (2017)
    The mitochondria-endoplasmic reticulum contact sites: a signalling platform for cell death
    Curr Opin Cell Biol 47, 52-63. doi:10.1016/j.ceb.2017.03.007
  5. Sood, A. et al. (2014)
    A Mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver
    Proc Natl Acad Sci U S A 111, 16017-16022. doi:10.1073/pnas.1408061111
  6. Prudent, J. et al. (2015)
    MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death
    Mol Cell 59, 941-955. doi:10.1016/j.molcel.2015.08.001

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