Balance of Mitochondrial Fission and Fusion

Other than playing a central role in energetics, mitochondria are also crucial for cellular redox balance, calcium homeostasis, lipid modification and regulation of cell death in various developmental contexts. Mitochondrial structure has been found to be dynamic particularly in various proliferating cells. They exist in different inter-convertible forms resulting from fission-fusion events between individual mitochondria, significance of which is far from clear. Currently, we are focused on understanding the significance of mitochondrial dynamism in cell proliferation and differentiation. A set of proteins that govern either fusion or fission of mitochondrial inner and outer membranes have been characterized and it is their activities that decide the steady state mitochondrial morphology in a cell; when fission dominates mitochondria remain as small fragmented elements and when fusion dominates mitochondria coalesced into larger hyperfused forms. In mitotic cells the key cell cycle regulators modulate mitochondrial morphology during progression through a mitotic cycle, which in turn modulates cell cycle. We use various kinds of biochemical, cell biological, microscopy and genetic tools to understand if the mitochondrial fission-fusion proteins can regulate cell proliferation, deregulation of which could initiate or maintain tumorigenic processes. We use our favorite model systems, mammalian cell lines and Drosophila, in a complementary fashion. Find snippets from some of our publications below. 

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Identification of cell cycle related mitochondrial hyperfusion

One method to study mitochondrial structure-function in live Drosophila tissue using ex vivo microscopy

Drp1 driven mitochondrial fission and Cell Cycle

Drp1-CellCycle co-expression module, and others, in various tumor tissues.

Cyclin E on the hyperfused mitochondria in Drp1 ablated cells

Inter-cellular heterogeneity of mitochondrial structure-function

Identification of mitochondria primed neoplastic stem cells

Dissociation of inverse relationship of mitochondrial [Fission] and [Fusion] metrics

'Goldilocks' level of repression of Drp1 driven mitochondrial fission primes a stem/progenitor cell state and thus supports neoplastic transformation