PMID- 35269529
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20220411
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 5
DP  - 2022 Mar 6
TI  - Direct Interaction of Mitochondrial Cytochrome c Oxidase with Thyroid Hormones: 
      Evidence for Two Binding Sites.
LID - 10.3390/cells11050908 [doi]
LID - 908
AB  - Thyroid hormones regulate tissue metabolism to establish an energy balance in the 
      cell, in particular, by affecting oxidative phosphorylation. Their long-term 
      impact is mainly associated with changes in gene expression, while the short-term 
      effects may differ in their mechanisms. Our work was devoted to studying the 
      short-term effects of hormones T2, T3 and T4 on mitochondrial cytochrome c 
      oxidase (CcO) mediated by direct contact with the enzyme. The data obtained 
      indicate the existence of two separate sites of CcO interaction with thyroid 
      hormones, differing in their location, affinity and specificity to hormone 
      binding. First, we show that T3 and T4 but not T2 inhibit the oxidase activity of 
      CcO in solution and on membrane preparations with K(i)  approximately  100-200 muM. In solution, 
      T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside to bind to 
      the enzyme. The peroxidase and catalase partial activities of CcO are not 
      sensitive to hormones, but electron transfer from heme a to the oxidized 
      binuclear center is affected. We believe that T3 and T4 could be ligands of the 
      bile acid-binding site found in the 3D structure of CcO by Ferguson-Miller's 
      group, and hormone-induced inhibition is associated with dysfunction of the 
      K-proton channel. A possible role of this interaction in the physiological 
      regulation of the enzyme is discussed. Second, we find that T2, T3, and T4 
      inhibit superoxide generation by oxidized CcO in the presence of excess H(2)O(2). 
      Inhibition is characterized by K(i) values of 0.3-5 muM and apparently affects the 
      formation of O(2)(●-) at the protein surface. The second binding site for thyroid 
      hormones presumably coincides with the point of tight T2 binding on the Va 
      subunit described in the literature.
FAU - Oleynikov, Ilya P
AU  - Oleynikov IP
AD  - A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow 
      State University, Leninskie Gory 1, Bld. 40, 119992 Moscow, Russia.
FAU - Sudakov, Roman V
AU  - Sudakov RV
AD  - N.N. Blokhin Russian Cancer Research Center, Kashirskoye Shosse 24, 115478 
      Moscow, Russia.
FAU - Azarkina, Natalia V
AU  - Azarkina NV
AD  - A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow 
      State University, Leninskie Gory 1, Bld. 40, 119992 Moscow, Russia.
FAU - Vygodina, Tatiana V
AU  - Vygodina TV
AUID- ORCID: 0000-0002-6373-3071
AD  - A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow 
      State University, Leninskie Gory 1, Bld. 40, 119992 Moscow, Russia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220306
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Thyroid Hormones)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Binding Sites
MH  - Electron Transport
MH  - *Electron Transport Complex IV/metabolism
MH  - *Hydrogen Peroxide/metabolism
MH  - Thyroid Hormones/metabolism
PMC - PMC8909594
OTO - NOTNLM
OT  - bile acid-binding site
OT  - cytochrome oxidase
OT  - regulation
OT  - steroid hormones
OT  - superoxide generation
OT  - thyroid hormones
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript or in the decision to publish the results.
EDAT- 2022/03/11 06:00
MHDA- 2022/04/12 06:00
PMCR- 2022/03/06
CRDT- 2022/03/10 15:34
PHST- 2022/01/19 00:00 [received]
PHST- 2022/02/23 00:00 [revised]
PHST- 2022/03/03 00:00 [accepted]
PHST- 2022/03/10 15:34 [entrez]
PHST- 2022/03/11 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2022/03/06 00:00 [pmc-release]
AID - cells11050908 [pii]
AID - cells-11-00908 [pii]
AID - 10.3390/cells11050908 [doi]
PST - epublish
SO  - Cells. 2022 Mar 6;11(5):908. doi: 10.3390/cells11050908.