hFis1, a Novel Component of the Mammalian Mitochondrial Fission Machinery*

By D. James, P. Parone, Yves Mattenberger, J. Martinou. Journal of Biological Chemistry, 2003

670 citations recorded by the source corpus.

The balance between the fission and fusion mechanisms regulate the morphology of mitochondria. In this study we have identified a mammalian protein that we call hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division. hFis1, when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission. This event was inhibited by a dominant negative mutant of Drp1 (Drp1(K38A)), a major component of the fission apparatus. Fragmentation of the mitochondrial network by hFis1 was followed by the release of cytochrome c and ultimately apoptosis. Bcl-xL was able to block cytochrome c release and apoptosis but failed to prevent mitochondrial fragmentation. Our studies show that hFis1 is part of the mammalian fission machinery and suggest that regulation of the fission processes might be involved in apoptotic mechanisms.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/19d2b6f741d7026a8851885cfaf4a50ca1559f38

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Citations in the corpus

The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. (2008, background): “These results are different from those obtained previously with Fis1 overexpression, which does cause fission (James et al., 2003; Yoon et al., 2003), but similar to results obtained with Drp1 overexpression, which does not cause fission (Smirnova et al., 2001).”
Mitochondrial dynamics and apoptosis. (2008, positive): “Fis1 overexpression induces mitochondrial fission and apoptosis (James et al. 2003), further linking Fis1 and cell death.”
Mitochondrial fission in apoptosis (2005, background): “, whereas overexpression of FIS1 induces cell deat”
Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. (2004, background): “, 2003), the two do not seem to stably associate (James et al., 2003) nor does overexpression of hFis1 increase Drp1 binding to mitochondria (Suzuki et al.”
Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. (2006, background): “In mammals, fission is con- trolled by the dynamin-related protein DRP-1 (Smirnova et al., 2001) and its outer membrane (OM) adaptor hFis1 (James et al., 2003; Yoon et al., 2003).”
Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease (2012, background): “Fission thus occurs when DLP1 oligomerizes into large ring-like complexes circling the future fission site along the mitochondrial outer surface to physically pinch a mitochondrion into two daughter mitochondria [38,43].”
Nitric oxide‐induced mitochondrial fission is regulated by dynamin‐related GTPases in neurons (2006, background): “To test whether mitochondrial fission plays a causal role in NO-mediated neurotoxicity, the expression levels of Drp1, Fis1 and Mfn1 in primary neurons were manipulated.”
Mitochondrial dynamics in mammalian health and disease. (2009, background): “Its pattern of localization, as shown by immunofluorescence, clearly differs from that of DRP1, as FIS1 signal is dispersed throughout the mitochondrial network (148, 285, 325).”
OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. (2006, positive): “Dynamin-related protein 1 (DRP-1) is located in the cytoplasm but during fission translocates to mitochondria where it binds to hFis1, its adaptor in the OM (Smirnova et al., 2001; Yoon et al., 2003; James et al., 2003).”
Mitochondrial fusion and fission in mammals. (2006, background): “Extension of these studies into mammalian cells has identified dynamin-related protein 1 (Drp1) and Fis1 as components of the mammalian mitochondrial fission machinery (James et al. 2003, Smirnova et al. 2001, Yoon et al. 2003).”
The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice (2009, background): “Most Drp1 is cytosolic and is recruited to the surface of mitochondria by proteins such as Fis1p/Fis1, Mdv1p, Caf4p, and Num1p (Mozdy et al., 2000; Tieu and Nunnari, 2000; Cerveny et al., 2001; James et al., 2003; Yoon et al., 2003: Griffin et al., 2005; Cerveny et al., 2007b).”
Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells (2010, background): “Because mammalian Fis1 was previously shown to induce mitochondrial fission (James et al., 2003; Yoon et al., 2003), we re-”
The BCL-2 Family Reunion (2010, background): “Downregulation of Fis1 also inhibits apoptosis, while its overexpression triggers mitochondrial fission and MOMP (James et al., 2003; Lee et al., 2004).”