PMID- 33287231 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20210624 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 12 DP - 2020 Dec 3 TI - The Interplay among Subunit Composition, Cardiolipin Content, and Aggregation State of Bovine Heart Cytochrome c Oxidase. LID - 10.3390/cells9122588 [doi] LID - 2588 AB - Mitochondrial cytochrome c oxidase (CcO) is a multisubunit integral membrane complex consisting of 13 dissimilar subunits, as well as three to four tightly bound molecules of cardiolipin (CL). The monomeric unit of CcO is able to form a dimer and participate in the formation of supercomplexes in the inner mitochondrial membrane. The structural and functional integrity of the enzyme is crucially dependent on the full subunit complement and the presence of unperturbed bound CL. A direct consequence of subunit loss, CL removal, or its oxidative modification is the destabilization of the quaternary structure, loss of the activity, and the inability to dimerize. Thus, the intimate interplay between individual components of the complex is imperative for regulation of the CcO aggregation state. While it appears that the aggregation state of CcO might affect its conformational stability, the functional role of the aggregation remains unclear as both monomeric and dimeric forms of CcO seem to be fully active. Here, we review the current status of our knowledge with regard to the role of dimerization in the function and stability of CcO and factors, such as subunit composition, amphiphilic environment represented by phospholipids/detergents, and posttranslational modifications that play a role in the regulation of the CcO aggregation state. FAU - Sedlak, Erik AU - Sedlak E AUID- ORCID: 0000-0003-1290-5774 AD - Center for Interdisciplinary Biosciences, P. J. Safarik University, Jesenna 5, 040 01 Kosice, Slovakia. FAU - Kozar, Tibor AU - Kozar T AD - Center for Interdisciplinary Biosciences, P. J. Safarik University, Jesenna 5, 040 01 Kosice, Slovakia. FAU - Musatov, Andrey AU - Musatov A AUID- ORCID: 0000-0001-8991-2468 AD - Department of Biophysics, Institute of Experimental Physics, Watsonova 47, 040 01 Kosice, Slovakia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20201203 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Cardiolipins) RN - 0 (Phospholipids) RN - 0 (Protein Subunits) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Animals MH - Cardiolipins/*metabolism MH - Electron Transport Complex IV/*metabolism MH - Heart/*physiology MH - Humans MH - Mitochondria/metabolism MH - Phospholipids/metabolism MH - Protein Subunits/*metabolism PMC - PMC7761698 OTO - NOTNLM OT - aggregations state OT - cardiolipin OT - cytochrome c oxidase OT - posttranslational modifications COIS- The authors declare no conflict of interest. EDAT- 2020/12/09 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/12/03 CRDT- 2020/12/08 01:07 PHST- 2020/10/28 00:00 [received] PHST- 2020/11/24 00:00 [revised] PHST- 2020/12/01 00:00 [accepted] PHST- 2020/12/08 01:07 [entrez] PHST- 2020/12/09 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/12/03 00:00 [pmc-release] AID - cells9122588 [pii] AID - cells-09-02588 [pii] AID - 10.3390/cells9122588 [doi] PST - epublish SO - Cells. 2020 Dec 3;9(12):2588. doi: 10.3390/cells9122588.