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Intramolecular regulation of Fis1 activity in fission and mitophagy
Author(s) -
Ihenacho Ugochukwu,
Egner John,
Harwig Megan,
Hill Blake
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04896
Subject(s) - fis1 , mitophagy , microbiology and biotechnology , yeast , chemistry , fission , mitochondrial fission , function (biology) , biology , biochemistry , gene , apoptosis , physics , autophagy , mitochondrial fusion , mitochondrial dna , quantum mechanics , neutron
Since its initial identification in yeast, Fis1, a 17kDa mitochondria‐outer‐membrane protein has been implicated in mitochondrial dynamics, mitophagy, and apoptosis. Despite this importance, the mechanisms by which Fis1 activity is governed in these processes remain unclear. Structural considerations suggests that a highly flexible N‐terminal “arm” may mediate interactions with cognate binding partners. We recently demonstrated that the human Fis1 arm, contrary to previous reports, is capable of assuming conformations akin to its distant relative, yeast Fis1p, suggesting a conserved mode of activity regulation across kingdoms. With this premise, we searched for amino acid sequences using structure and homology‐based sequence alignments, which identified a uniquely conserved region that we hypothesize to be important for regulating Fis1 function. Using MD simulations, IF‐microscopy, and NMR, we show that this region is important for Fis1 fission and mitophagic function.