Mitochondrial kinases and their molecular interaction with cardiolipin.
Mitochondrial isoforms of creatine kinase (MtCK) and nucleoside diphosphate kinase (NDPK-D) are not phylogenetically related but share functionally important properties. They both use mitochondrially generated ATP with the ultimate goal of maintaining proper nucleotide pools, are located in the intermembrane/cristae space, have symmetrical oligomeric structures, and show high affinity binding to anionic phospholipids, in particular cardiolipin. The structural basis and functional consequences of the cardiolipin interaction have been studied and are discussed in detail in this review. They mainly result in a functional interaction of MtCK and NDPK-D with inner membrane adenylate translocator, probably by forming proteolipid complexes. These interactions allow for privileged exchange of metabolites (channeling) that ultimately regulate mitochondrial respiration. Further functions of the MtCK/membrane interaction include formation of cardiolipin membrane patches, stabilization of mitochondria and a role in apoptotic signaling, as well as in case of both kinases, a role in facilitating lipid transfer between two membranes. Finally, disturbed cardiolipin interactions of MtCK, NDPK-D and other proteins like cytochrome c and truncated Bid are discussed more generally in the context of apoptosis and necrosis.
Schlattner
Uwe
U
University Joseph Fourier, Grenoble, F-38041, France. uwe.schlattner@ujf-grenoble.fr
Tokarska-Schlattner
Malgorzata
M
Ramirez
Sacnicte
S
Brückner
Anna
A
Kay
Laurence
L
Polge
Cécile
C
Epand
Raquel F
RF
Lee
Ray M
RM
Lacombe
Marie-Lise
ML
Epand
Richard M
RM
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D052281:Creatine Kinase, Mitochondrial Form / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*
D002308:Cardiolipins; D052281:Creatine Kinase, Mitochondrial Form; D009701:Nucleoside-Diphosphate Kinase