The @entity1 homologue of @entity375 XXXX ATPase (Lactation elevated 1) mediates degradation of nuclear-encoded complex IV subunits.

@entity1 @entity71834 @entity47075 @entity45811 @entity55605 @entity72703 @entity72702 @entity375 @entity72704 @entity19976
UNASSIGNED: Mitochondrial protein homeostasis is crucial for cellular function and integrity and is therefore maintained by several classes of proteins possessing chaperone and/or proteolytic activities. In this work we focused on characterization of @entity47075 (lactation elevated 1) function in mitochondrial protein homeostasis maintenance. @entity47075 is the @entity1 homologue of @entity375 mitochondrial @entity72702 ATPase, a member of SEC18-NSF, @entity72703 , @entity19976 -VCP, TBP family. @entity375 @entity72702 was shown to mediate degradation of mitochondrially-encoded complex IV subunits, and based on its similarity with @entity19976 (p97/VCP) it was suggested to facilitate extraction of polytopic membrane proteins. Here we show that @entity47075 , which is a mitochondrial integral membrane protein, exists as part of three complexes of approx. 140, 400 and 500 kDa and is essential for maintenance of fused mitochondrial reticulum and lamellar cristae morphology. We demonstrate that @entity47075 mediates degradation of nuclear-encoded complex IV subunits @entity45811 , @entity55605 and COX6A, and is required for normal activity of complexes III and IV of respiratory chain. Using affinity purification of @entity47075 -FLAG expressed in @entity47075 knockdown background we show that the protein physically interacts with @entity45811 and @entity55605 subunits of complex IV and with mitochondrial inner-membrane protease YME1L. Finally, we demonstrate by ectopic expression of both @entity71834 Walker A and @entity72704 Walker B mutants, that an intact ATPase domain is essential for @entity47075 -mediated degradation of nuclear-encoded complex IV subunits. Thus, our work establishes @entity47075 as a novel factor with crucial role in mitochondrial protein homeostasis maintenance.
