Investigating post-translational modifications of Mitochondrial Fission Factor and their effects on mitochondrial dynamics (360G-Wellcome-109304_Z_15_A)

£19,175

Mitochondria exist as a cellular-wide, dynamic network, which changes according to the stress and energetic state of the cell. Mitochondria are constantly undergoing fusion and fission cycles, a means of quality control; healthy mitochondria fuse with the network, whereas those unable to maintain membrane potential are targeted for mitophagy. The major fission machinery consists of a transmembrane protein in the outer membrane of the mitochondria, mitochondrial fission factor (Mff), and dynamin-related protein 1 (Drp1), which is recruited to Mff from the cytosol to initiate fission. Drp1 is subject to extensive post-translational modifications (PTM), which alters its recruitment to mitochondria. Mff is also post-translationally modified, but little is known about the biological outcomes. We recently identified a SUMOylation site on Mff, and show that phosphorylation enhances SUMOylation. Our hypothesis is that these PTMs play critical roles in regulating physiological and pathophysiological fission that, among other things, may be involved in the aetiology of neurodegenerative diseases. Using phosphorylation, SUMOylation and ubiquitination deficient mutants, we will systemically investigate how these PTMs of Mff affect 1) Drp1 binding, 2) SUMOylation, 3) mitochondrial fission and morphology, 4) the reciprocal interactions between these modifications, and 5) their involvement in responses to cell stress in neurodegenerative disease.

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Grant Details

Amount Awarded 19175
Applicant Surname Seager
Approval Committee Internal Decision Panel
Award Date 2017-01-31T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title PhD Studentship (Basic)
Internal ID 109304/Z/15/A
Lead Applicant Mr Richard Seager
Partnership Value 19175
Planned Dates: End Date 2018-10-01T00:00:00+00:00
Planned Dates: Start Date 2015-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South West