TY  - JOUR
A1  - Garlich, Joshua
A1  - Strecker, Valentina
A1  - Wittig, Ilka
A1  - Stuart, Rosemary A.
T1  - Mutational Analysis of the QRRQ Motif in the Yeast Hig1 Type 2 Protein Rcf1 Reveals a Regulatory Role for the Cytochrome c Oxidase Complex
T2  - Journal of biological chemistry
N2  - The yeast Rcf1 protein is a member of the conserved family of proteins termed the hypoxia-induced gene (domain) 1 (Hig1 or HIGD1) family. Rcf1 interacts with components of the mitochondrial oxidative phosphorylation system, in particular the cytochrome bc1 (complex III)-cytochrome c oxidase (complex IV) supercomplex (termed III-IV) and the ADP/ATP carrier proteins. Rcf1 plays a role in the assembly and modulation of the activity of complex IV; however, the molecular basis for how Rcf1 influences the activity of complex IV is currently unknown. Hig1 type 2 isoforms, which include the Rcf1 protein, are characterized in part by the presence of a conserved motif, (Q/I)X3(R/H)XRX3Q, termed here the QRRQ motif. We show that mutation of conserved residues within the Rcf1 QRRQ motif alters the interactions between Rcf1 and partner proteins and results in the destabilization of complex IV and alteration of its enzymatic properties. Our findings indicate that Rcf1 does not serve as a stoichiometric component, i.e. as a subunit of complex IV, to support its activity. Rather, we propose that Rcf1 serves to dynamically interact with complex IV during its assembly process and, in doing so, regulates a late maturation step of complex IV. We speculate that the Rcf1/Hig1 proteins play a role in the incorporation and/or remodeling of lipids, in particular cardiolipin, into complex IV and. possibly, other mitochondrial proteins such as ADP/ATP carrier proteins.
KW  - bioenergetics
KW  - cardiolipin
KW  - cytochrome c oxidase (complex IV)
KW  - mitochondria
KW  - yeast
KW  - Hig1
KW  - Rcf1
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77367
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-773673
SN  - 0021-9258
VL  - 292.2017
IS  - 13
SP  - 5216
EP  - 5226
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -