Linked Life Data

21160028

Source:http://linkedlifedata.com/resource/pubmed/id/21160028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-1
pubmed:abstractText
Recent studies have shown mitochondrial fragmentation during cell stress and have suggested a role for the morphological change in mitochondrial injury and ensuing apoptosis. However, the underlying mechanism remains elusive. Here we demonstrate that mitochondrial fragmentation facilitates Bax insertion and activation in mitochondria, resulting in the release of apoptogenic factors. In HeLa cells, overexpression of mitofusins attenuated mitochondrial fragmentation during cisplatin- and azide-induced cell injury, which was accompanied by less apoptosis and less cytochrome c release from mitochondria. Similar effects were shown by inhibiting the mitochondrial fission protein Drp1 with a dominant negative mutant (dn-Drp1). Mitofusins and dn-Drp1 did not seem to significantly affect Bax translocation/accumulation to mitochondria; however, they blocked Bax insertion and activation in mitochondrial membrane. Consistently, in rat kidney proximal tubular cells, small interfering RNA knockdown of Drp1 prevented mitochondrial fragmentation during azide-induced ATP depletion, which was accompanied by less Bax activation, insertion, and oligomerization in mitochondria. These cells released less cytochrome c and AIF from mitochondria and showed significantly lower apoptosis. Finally, mitofusin-null mouse embryonic fibroblasts (MEF) had fragmented mitochondria. These MEFs were more sensitive to cisplatin-induced Bax activation, release of cytochrome c, and apoptosis. Together, this study provides further support for a role of mitochondrial fragmentation in mitochondrial injury and apoptosis. Mechanistically, mitochondrial fragmentation may sensitize the cells to Bax insertion and activation in mitochondria, facilitating the release of apoptogenic factors and consequent apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1522-1563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C447-55
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21160028-Animals, pubmed-meshheading:21160028-Apoptosis, pubmed-meshheading:21160028-Apoptosis Regulatory Proteins, pubmed-meshheading:21160028-Cell Line, pubmed-meshheading:21160028-Cells, Cultured, pubmed-meshheading:21160028-Enzyme Activation, pubmed-meshheading:21160028-GTP Phosphohydrolases, pubmed-meshheading:21160028-Gene Knockdown Techniques, pubmed-meshheading:21160028-HeLa Cells, pubmed-meshheading:21160028-Humans, pubmed-meshheading:21160028-Membrane Fusion, pubmed-meshheading:21160028-Membrane Transport Proteins, pubmed-meshheading:21160028-Mice, pubmed-meshheading:21160028-Mice, Knockout, pubmed-meshheading:21160028-Microtubule-Associated Proteins, pubmed-meshheading:21160028-Mitochondria, pubmed-meshheading:21160028-Mitochondrial Diseases, pubmed-meshheading:21160028-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:21160028-Mitochondrial Proteins, pubmed-meshheading:21160028-RNA Interference, pubmed-meshheading:21160028-Rats, pubmed-meshheading:21160028-Stress, Physiological, pubmed-meshheading:21160028-bcl-2-Associated X Protein
pubmed:year
2011
pubmed:articleTitle
Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis.
pubmed:affiliation
Dept. of Cellular Biology and Anatomy, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural