Mitochondrial fission is crucial for cristae remodeling
نویسنده
چکیده
< a d d a r t t y p e = " r e l " d o i = " 1 0. 1 0 8 3 / j c b. 2 0 1 5 0 8 0 9 9 " > Otera et al.< / a d d a r t > reveal that the mito-chondrial fi ssion factor Drp1 and its receptors MiD49 and MiD51 promote apoptosis by remodeling mitochondrial cristae. Early in apoptosis, mitochon-drial cristae are remodeled so that cytochrome c enters the space between the inner and outer mito-chondrial membranes, from where it can be released into the cytoplasm to initiate caspase activation and cell death. Cristae remodeling is facilitated by mitochondrial fi ssion, a process driven by the dynamin-like GTPase Drp1 and its receptors on the outer mitochondrial membrane. Whether Drp1-mediated fi ssion is required for cytochrome c release remains unclear, however. Otera et al. found that three Drp1 receptors—Mff, MiD49, and MiD51—have redundant roles in recruiting Drp1 and promoting mitochondrial fi ssion. Knocking out Mff had little effect on cytochrome c release in apoptotic cells, but deleting MiD49, MiD51, or Drp1 itself prevented cristae remodeling and cytochrome c release during the early stages of apoptosis. Cristae are thought to be stabilized by protein complexes containing long and short isoforms of the GTPase OPA1, and apoptotic signals are thought to induce cristae remodeling by initiating the proteolytic processing and disassembly of these complexes. Surprisingly, however, OPA1 complexes were still disrupted in remodeling-resistant MiD49/MiD51 knockout cells, indicating that OPA1 processing isn't suffi cient to induce cristae reorganization. Instead, says senior author Katsuyoshi Mihara, the results demonstrate a critical role for Drp1-mediated mitochondrial fi ssion. The authors now want to investigate how MiD49 and MiD51 might interact with the cristae remodeling machinery. < a d d a r t t y p e = " r e l " d o i = " 1 0. 1 0 8 3 / j c b. 2 0 1 5 0 7 0 2 3 " > Wang et al.< / a d d a r t > explain why loss of the autophagy-initiating protein Fip200 alters the fate of neural stem cells (NSCs). Fip200 is required to induce the formation of autophago-somes that engulf and recycle cytoplasmic components. NSCs lacking Fip200 fail to self-renew or differentiate properly, possibly because, in the absence of autophagy, they accumulate mito-chondria …
منابع مشابه
Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling
Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed the functional division of these receptors with their knockout (KO) cell lines. In marked contras...
متن کاملDrp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling
Cytochrome c release from the cristae into the cytoplasm constitutes the key step of intrinsic apoptosis (Frank et al., 2001; Detmer and Chan, 2007). A majority of total cytochrome c is encapsulated within the mitochondrial cristae folds that are connected to the intermembrane space (IMS) by relatively narrow structures named cristae junctions. At the early phase of intrinsic apoptosis, apoptot...
متن کاملThe i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission
Mitochondrial fusion and structure depend on the dynamin-like GTPase OPA1, whose activity is regulated by proteolytic processing. Constitutive OPA1 cleavage by YME1L and OMA1 at two distinct sites leads to the accumulation of both long and short forms of OPA1 and maintains mitochondrial fusion. Stress-induced OPA1 processing by OMA1 converts OPA1 completely into short isoforms, inhibits fusion,...
متن کاملMitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli
Huntington's disease (HD), a genetic neurodegenerative disease caused by a polyglutamine expansion in the Huntingtin (Htt) protein, is accompanied by multiple mitochondrial alterations. Here, we show that mitochondrial fragmentation and cristae alterations characterize cellular models of HD and participate in their increased susceptibility to apoptosis. In HD cells, the increased basal activity...
متن کاملMitochondrial Rhomboid PARL Regulates Cytochrome c Release during Apoptosis via OPA1-Dependent Cristae Remodeling
Rhomboids, evolutionarily conserved integral membrane proteases, participate in crucial signaling pathways. Presenilin-associated rhomboid-like (PARL) is an inner mitochondrial membrane rhomboid of unknown function, whose yeast ortholog is involved in mitochondrial fusion. Parl-/- mice display normal intrauterine development but from the fourth postnatal week undergo progressive multisystemic a...
متن کامل