Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance.

Journal of Cell Science
Vassilios N KotiadisCampbell W Gourlay

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.

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Citations

Sep 11, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Matheus BeckerFábio Klamt
Aug 11, 2012·Bioarchitecture·Melissa DesouzaJustine R Stehn
Oct 25, 2013·FEMS Yeast Research·Daniel G J SmethurstCampbell W Gourlay
Feb 14, 2016·Cytoskeleton·James R Bamburg, Barbara W Bernstein
Jul 1, 2019·Biological Chemistry·Lena HoffmannCarsten Culmsee
Aug 27, 2019·Frontiers in Aging Neuroscience·Yingni SunHongwei Gao

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