Reference: Kotiadis VN, et al. (2012) Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance. J Cell Sci 125(Pt 9):2288-99

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Abstract


ADF/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast Saccharomyces cerevisiae. Our data link surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras, respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity lead to a dramatic increase in respiratory function that triggers a retrograde signal to upregulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Kotiadis VN, Leadsham JE, Bastow EL, Gheeraert A, Whybrew JM, Bard M, Lappalainen P, Gourlay CW
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