Cofilin(s) and Mitochondria: Function Beyond Actin Dynamics

ADF/cofilins form a family of small, widely expressed actin-binding proteins, regulating actin dynamics in various cellular and physiological processes in all eukaryotes from yeasts to animals. Changes in the expression of the ADF/cofilin family proteins have been demonstrated under various pathological conditions. The established role for cofilin in migration, invasion, epithelial-mesenchymal transition, apoptosis, radiotherapy and chemotherapy resistance, immune escape, and transcriptional dysregulation in malignant tumors, is explained mainly by its actin modifying activity. Moreover, drugs targeting this activity of cofilin were developed for treatment of cancers. Its multilevel regulation, extremely diverse effects in numerous forms of pathology, and the conflicting data on the functional effects of changes in cofilin expression prompted us here to point to other functions of cofilin, in addition to that of modifying actin, namely, those which affect lipid metabolism and mitochondrial homeostasis. Here, we review recent data on the expression of ADF/cofilin family proteins in various pathologies, account for the mutations and post-translational modifications of these proteins and their functional consequences, dwell on the role of K63-type ubiquitination of cofilin for its involvement in lipid metabolism and mitochondrial homeostasis, point out conflicting data in cofilin research, and describe prospects for future studies of cofilin functions.