Mitochondria frequently change their shape through fission and fusion in response to physiological stimuli as well as pathological insults. Disrupted mitochondrial morphology has been observed in @entity409 . However, the role of mitochondrial shape change in @entity1448 is not defined. In this study, using in vitro and in vivo models of @entity6741 -induced @entity99 , we investigated the contribution of mitochondrial morphology to the pathogenesis of @entity409 . We found that the toxic bile salt glycochenodeoxycholate (GCDC) rapidly fragmented mitochondria, both in primary @entity19 hepatocytes and in the bile transporter-expressing hepatic cell line McNtcp.24, leading to a significant increase in cell death. GCDC-induced @entity2383 was associated with an increase in reactive @entity26 species (ROS) levels. We found that preventing @entity2383 in GCDC by inhibiting mitochondrial fission significantly decreased not only ROS levels but also cell death. We also induced @entity1448 in @entity19 livers via common bile duct ligation. Using a transgenic @entity19 model inducibly expressing a dominant-negative fission mutant specifically in the liver, we demonstrated that decreasing mitochondrial fission substantially diminished ROS levels, @entity99 , and @entity82 under cholestatic conditions. Taken together, our results provide new evidence that controlling mitochondrial fission is an effective strategy for ameliorating @entity99 .

Decreasing mitochondrial fission prevents XXXX .

@entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity409 :: ('MESH:D008107', 'Disease') :: ['cholestatic liver disease'] @entity1448 :: ('MESH:D002779', 'Disease') :: ['cholestasis'] @entity6741 :: ('CHEBI:3098', 'Chemical') :: ['bile acid'] @entity99 :: ('MESH:D056486', 'Disease') :: ['liver injury', 'cholestatic liver injury'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial fragmentation']
@entity99 :: (MESH:D056486,Disease) :: ['cholestatic liver injury']
