Response by Arezu Jahani‐Asl & Ruth S. Slack

Abstract

Correspondence12 October 2007free access Response by Arezu Jahani-Asl & Ruth S. Slack Arezu Jahani-Asl Arezu Jahani-Asl Neuroscience Research Institute, University of Ottawa and Ottawa Health Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada Search for more papers by this author Ruth S Slack Corresponding Author Ruth S Slack Neuroscience Research Institute, University of Ottawa and Ottawa Health Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada Search for more papers by this author Arezu Jahani-Asl Arezu Jahani-Asl Neuroscience Research Institute, University of Ottawa and Ottawa Health Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada Search for more papers by this author Ruth S Slack Corresponding Author Ruth S Slack Neuroscience Research Institute, University of Ottawa and Ottawa Health Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada Search for more papers by this author Author Information Arezu Jahani-Asl1 and Ruth S Slack 1 1Neuroscience Research Institute, University of Ottawa and Ottawa Health Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada *Corresponding author. E-mail: [email protected] EMBO Reports (2007)8:1089-1090https://doi.org/10.1038/sj.embor.7401119 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info A recent study by Cribbs & Strack (2007) identified a new mechanism for the integration of the second messengers Ca2+ and cAMP in the regulation of mitochondria form and function. This study was the first to provide a mechanistic link between phosphorylation of dynamin-related protein 1 (Drp1)—a component of mitochondrial fission machinery—and the regulation of apoptosis. Our report also referred extensively to two previous studies that investigated the role of DRP1 phosphorylation in mitochondrial fission: one study published by Chang & Blackstone (2007a) also identified a cAMP-dependent protein kinase (PKA) phosphorylation site on human DRP1, and a report by Taguchi et al (2007) showed that DRP1 is phosphorylated by Cdk1/cyclin B (Cdk1 for cyclin-dependent kinase 1) in a cell-cycle-dependent manner. Together, these three studies provide evidence that the post-translational modification of DRP1 has a crucial role in the regulation of mitochondrial dynamics and cellular function. Chang & Blackstone (2007b) have responded to our report to clarify two points. First, they have provided a sequence alignment between the rat and human DRP1 sequence and have indicated that the PKA phosphorylation of DRP1 at Ser 656 in rat (reported by Cribbs & Strack, 2007) and Ser 637 in human (reported by Chang & Blackstone, 2007a) represent the same serine residue. Second, we had referred to the loss of GTPase activity in the Cribbs & Strack (2007) study where we should have described it as a loss of Drp1 fission activity. Therefore, although Drp1 activity and GTPase activity were interchangeably used, it is important to emphasize that in the Cribbs & Strack study no reduction in GTPase activity was shown, whereas the Chang & Blackstone (2007a) study did show a reduction in both fission and GTPase activity. Although we appreciate this clarification, we would like to re-emphasize that the crucial point of our Literature Report (Jahani-Asl & Slack, 2007) was to highlight the physiological relevance of PKA-mediated Drp1 phosphorylation that had not been previously shown. The findings of the Cribb & Strack (2007) paper bring the regulation of Drp1 phosphorylation into a broader context by showing its physiological importance for cell death. Understanding the physiological outcomes of post-translational modifications such as phosphorylation in the context of cellular function—including apoptosis and cell cycle regulation—is the ultimate challenge for cell biologists. Biography Arezu Jahani-Asl and Ruth S. Slack are at the Neuroscience Research Institute, University of Ottawa and Ottawa Health Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada References Chang CR, Blackstone C (2007a) Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J Biol Chem 282: 21583–21587CrossrefCASPubMedWeb of Science®Google Scholar Chang CR, Blackstone C (2007b) Drp1 phosphorylation and mitochondrial regulation. EMBO Rep 8: 1088–1089Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Cribbs JT, Strack S (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8: 939–944Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Jahani-Asl A, Slack RS (2007) The phosphorylation state of Drp1 determines cell fate. EMBO Rep 8: 912–913Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Taguchi N, Ishihara N, Jokufu A, Oka T, Mihara K (2007) Mitotic phosphorylation of dynamin-related GTPase participates in mitochondrial fission. J Biol Chem 282: 11521–11529CrossrefCASPubMedWeb of Science®Google Scholar Previous ArticleNext Article Volume 8Issue 121 December 2007In this issue ReferencesRelatedDetailsLoading ...