Abstract
Mitochondrial fission is a highly regulated process mediated by a defined set of protein factors and is involved in the early stage of apoptosis. In mammals, at least two proteins, the dynamin-like protein DLP1/Drp1 and the mitochondrial outer membrane protein hFis1, participate in mitochondrial fission. The cytosolic domain of hFis1 contains six alpha-helices that form two tetratricopeptide repeat (TPR) motifs. Overexpression of hFis1 induces DLP1-mediated fragmentation of mitochondria, suggesting that hFis1 is a limiting factor in mitochondrial fission by recruiting cytosolic DLP1. In the present study, we identified two regions of hFis1 that are necessary for correct fission of mitochondria. We found that the TPR region of hFis1 participates in the interaction with DLP1 or DLP1-containing complex and that the first helix (alpha1) of hFis1 is required for mitochondrial fission presumably by regulating DLP1-hFis1 interaction. Misregulated interaction between DLP1 and hFis1 by alpha1 deletion induced mitochondrial swelling, in part by the mitochondrial permeability transition, but significantly delayed cell death. Our data suggest that hFis1 is a main regulator of mitochondrial fission, controlling the recruitment and assembly of DLP1 during both normal and apoptotic fission processes.
Highlights
Mitochondria in mammalian cells frequently change their shapes by fission and fusion (Bereiter-Hahn, 1990; BereiterHahn and Voth, 1994)
We found that the mitochondrial fraction from cells hFis1 in mitochondrial fission and apoptosis 4147 transfected with hFis1[32-152] contained increased DLP1 compared with that of untransfected cells after normalization (Fig. 5B)
We found that the interaction between full-length hFis1 and DLP1 is extremely week and/or transient (Yoon et al, 2003), and that, in this report, deletion of the first ␣-helix of hFis1 increases the interaction with DLP1 while losing the ability to promote mitochondrial fission
Summary
Mitochondria in mammalian cells frequently change their shapes by fission and fusion (Bereiter-Hahn, 1990; BereiterHahn and Voth, 1994). A set of proteins that participate in mitochondrial fission has been identified in yeast and mammals (Cerveny et al, 2001; James et al, 2003; Karbowski et al, 2004; Mozdy et al, 2000; Otsuga et al, 1998; Pitts et al, 1999; Smirnova et al, 1998; Tieu and Nunnari, 2000; Yoon et al, 2003) One of these proteins, DLP1/Drp in mammals and Dnm1p in yeast, is a member of the dynamin family of large GTPases and mediates the scission of mitochondrial membranes through GTP hydrolysis.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
