Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10415 (
Bcl-2
)
33,771
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis, tBid is targeted to mitochondria and causes cytochrome c release. We investigated the regulation of tBid-induced cytochrome c release and apoptosis by
phospholipid scramblase 3
(
PLS3
). Overexpression of
PLS3
enhanced, whereas downregulation of
PLS3
delayed, TNF-alpha-induced apoptosis and targeting of tBid to mitochondria. On the basis of the theory that tBid targets mitochondrial cardiolipin, we hypothesize that
PLS3
enhances translocation of cardiolipin to the mitochondrial surface to facilitate tBid targeting. NAO, a cardiolipin binding dye, was first used to quantify the distribution of cardiolipin. Overexpression of
PLS3
increases, whereas downregulation of
PLS3
decreases, the percentage of cardiolipin on the mitochondrial surface. Determination of the tBid binding capacity on the mitochondrial surface by FITC-labeled tBid(G94E) also confirmed that tBid binding capacity increased upon
PLS3
overexpression and decreased with downregulation of
PLS3
.
PLS3
activity, determined by a lipid flip-flop assay, was activated by calcium and tBid but inhibited by
Bcl-2
. Mutation of the calcium binding motif abolishes the lipid flip-flop activity of
PLS3
.
PLS3
and tBid may form a bidirectional positive feedback loop that is antagonized by
Bcl-2
. Overexpression of
PLS3
does not affect mitochondrial potential but does interfere with mitochondrial respiration and production of reactive oxygen species. These studies thus establish
PLS3
as an important downstream effector of
Bcl-2
and tBid in apoptosis.
...
PMID:Role of phospholipid scramblase 3 in the regulation of tumor necrosis factor-alpha-induced apoptosis. 1835 5
Mitochondria, besides playing a central role in energy metabolism within the cell, are involved in a cohort of other processes like cellular differentiation and apoptosis. Investigations during recent few years have shown that protein kinases, including PKA, PKB/Akt, PKC, Raf-1, p38 MAPK, JNK, ERK1/2, Src, Fyn and Csk, may directly interact with mitochondrial proteins. Their role mainly concentrates at phosphorylation of pro- and anti-apoptotic proteins (Bad, Bax,
Bcl-2
, Bcl-xL), phosphorylation/modification of electron transport chain proteins (complex I, COIV), MPTP forming proteins VDAC and ANT, proteins of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) and
phospholipid scramblase 3
(
PLSCR3
). Many experimental data showed the presence of protein kinases in the outer and inner mitochondrial membranes as well as in the mitochondrial matrix during in vitro cell stimulations, in neurodegenerative diseases and in in vivo ischaemia heart preconditioning. These data show that translocation of protein kinases to mitochondria plays an important role especially during ischaemia/reperfusion in brain and heart.
...
PMID:[Protein kinases in mitochondria]. 1880 32
