– Abstract –
The role of F-actin binding protein Cotl1 in regulation of mitochondrial dynamics
Mitochondrial fission and fusion are important in maintaining normal cell physiology, and regulated by mitochondrial-shaping proteins, including Drp1, Fis1, Mfn1, Mfn2, and Opa1. Dynamic interaction between mitochondria and cytoskeleton is important for maintaining mitochondrial function and structure. F-actin, a major component of cytoskeleton, is essential in cell stability and morphogenesis.
In this study, I investigated whether Coactosine-like protein 1 (Cotl1), an F-actin-binding protein, is involved in mitochondrial morphology regulation. The Cotl1 was selected as a candidate for elucidating mitochondria and cytoskeleton network regulatory molecule via the differential display method of whole gene expression among three types of cells with different mitochondrial morphology.
Cellular localization analysis revealed predominant, endogenous Cotl1 overexpression in the cytosol. However, in Drp1-depleted cells, mitochondria were elongated owing to fission inhibition and mitochondrial co-localization of Cotl1 significantly increased.
Knockdown of Cotl1 resulted in significantly elongated mitochondria, abnormal F-actin morphology, and increased mitochondrial F-actin accumulation. Furthermore, confocal microscopy and transmission electron microscopy analyses demonstrated that mitochondria of primary cultured heart cells derived from Cotl1-knockout mouse were significantly elongated compared to those from wild-type mouse. Moreover, Cotl1-knockdown cells and Cotl1-knockout heart cells showed increased Mfn1 and Mfn2 expression, and decreased phosphorylation of Drp1 at Serine 616 residue.
These results suggest a possible role of Cotl1 in mitochondrial fission and/or fusion process mediated by binding with F-actin.
