bims-cytox1 2022-11-27 papers

Issue of 2022‒11‒27
five papers selected by
Gavin McStay
Liverpool John Moores University

Int J Mol Sci. 2022 Nov 10. pii: 13880. [Epub ahead of print]23(22):

Mitochondrial Respiratory Chain Supercomplexes: From Structure to Function.

Mitochondrial oxidative phospho rylation, the center of cellular metabolism, is pivotal for the energy production in eukaryotes. Mitochondrial oxidative phosphorylation relies on the mitochondrial respiratory chain, which consists of four main enzyme complexes and two mobile electron carriers. Mitochondrial enzyme complexes also assemble into respiratory chain supercomplexes (SCs) through specific interactions. The SCs not only have respiratory functions but also improve the efficiency of electron transfer and reduce the production of reactive oxygen species (ROS). Impaired assembly of SCs is closely related to various diseases, especially neurodegenerative diseases. Therefore, SCs play important roles in improving the efficiency of the mitochondrial respiratory chain, as well as maintaining the homeostasis of cellular metabolism. Here, we review the structure, assembly, and functions of SCs, as well as the relationship between mitochondrial SCs and diseases.

Keywords: assembly; cytochrome c; mitochondria; respiratory chain; supercomplexes

DOI: https://doi.org/10.3390/ijms232213880

Int J Mol Sci. 2022 Nov 17. pii: 14241. [Epub ahead of print]23(22):

Pentatricopeptide Protein PTCD2 Regulates COIII Translation in Mitochondria of the HeLa Cell Line.

Maria V Baleva, Ivan Chicherin, Uliana Piunova, Viktor Zgoda, Maxim V Patrushev, Sergey Levitskii, Piotr Kamenski.

Protein biosynthesis in mitochondria is tightly coupled with assembly of inner membrane complexes and therefore must be coordinated with cytosolic translation of the mRNAs corresponding to the subunits which are encoded in the nucleus. Molecular mechanisms underlying the regulation of mitochondrial translation remain unclear despite recent advances in structural biology. Until now, only one translational regulator of protein biosynthesis in mammalian mitochondria is known-protein TACO1, which regulates translation of COI mRNA. Here we describe the function of pentatricopeptide-containing protein PTCD2 as a translational regulator of another mitochondrially encoded subunit of cytochrome c oxidase-COIII in the HeLa cell line. Deletion of the PTCD2 gene leads to significant decrease in COIII translation efficiency and impairment in CIV activity. Additionally, we show that PTCD2 protein is partially co-sedimentates with associated mitochondrial ribosome and associates with mitochondrial ribosome proteins in pull-down assays. These data allow concluding that PTCD2 is a specific translational regulator of COIII which attracts the mRNA to the mitochondrial ribosome.

Keywords: mitochondria; translation; translation regulation

DOI: https://doi.org/10.3390/ijms232214241

Biochim Biophys Acta Bioenerg. 2022 Nov 17. pii: S0005-2728(22)00403-0. [Epub ahead of print]1864(2): 148933

Structures of the intermediates in the catalytic cycle of mitochondrial cytochrome c oxidase.

Mårten Wikström, Robert B Gennis, Peter R Rich.

Keywords: Cell respiration; Heme‑copper oxidases; Oxygen reduction; Respiratory chain

DOI: https://doi.org/10.1016/j.bbabio.2022.148933

Biochim Biophys Acta Bioenerg. 2022 Nov 17. pii: S0005-2728(22)00407-8. [Epub ahead of print] 148937

Individual heme a and heme a3 contributions to the Soret absorption spectrum of the reduced bovine cytochrome c oxidase.

Artem V Diuba, Tatiana V Vygodina, Natalia V Azarkina, Alexander M Arutyunyan, Tewfik Soulimane, Marten H Vos, Alexander A Konstantinov.

Bovine cytochrome c oxidase (CcO) contains two hemes, a and a3, chemically identical but differing in coordination and spin state. The Soret absorption band of reduced aa3-type cytochrome c oxidase consists of overlapping bands of the hemes a2+ and a32+. It shows a peak at ~444 nm and a distinct shoulder at ~425 nm. However, attribution of individual spectral lineshapes to hemes a2+ and a32+ in the Soret is controversial. In the present work, we characterized spectral contributions of hemes a2+ and a32+ using two approaches. First, we reconstructed bovine CcO heme a2+ spectrum using a selective Ca2+-induced spectral shift of the heme a2+. Second, we investigated photobleaching of the reduced Thermus thermophilus ba3- and bovine aa3-oxidases in the Soret induced by femtosecond laser pulses in the Q-band. The resolved spectra show splitting of the electronic B0x-, B0y-transitions of both reduced hemes. The heme a2+ spectrum is shifted to the red relative to heme a32+ spectrum. The ~425 nm shoulder is mostly attributed to heme a32+.

Keywords: Absorption spectra; Cytochrome c oxidase; Femtosecond pump-probe spectroscopy

DOI: https://doi.org/10.1016/j.bbabio.2022.148937

Cell Death Dis. 2022 Nov 23. 13(11): 988

COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism.

Yetong Feng, Jiayi Xu, Mengjiao Shi, Rongrong Liu, Lei Zhao, Xin Chen, Miaomiao Li, Yaping Zhao, Jiahui Chen, Wenjing Du, Pengfei Liu.

COX7A1, a subunit of cytochrome c oxidase, holds an important position in the super-assembly which integrates into multi-unit heteromeric complexes peripherally in the mitochondrial electron transport chain (ETC). Recently, some studies indicated the significant potential of COX7A1 in cancer metabolism and therapy. However, the underlying metabolic process and therapy mechanism remain unclear. In this study, COX7A1-overexpressed cell line was established via lentivirus transduction. The relationship between COX7A1 and ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, was further analyzed in different human non-small-cell lung carcinoma (NSCLC) cells respectively. Our results showed that COX7A1 increased the sensitivity of NSCLC cells to the ferroptosis induced by cysteine deprivation via enhancing the tricarboxylic acid (TCA) cycle and the activity of complex IV in mitochondrial ETC. Meanwhile, COX7A1 suppressed mitochondrial dynamics as well as mitochondrial biogenesis and mitophagy through blocking autophagic flux. The autophagy activator, rapamycin, relieved the autophagic blockage and further strengthened the sensitivity to cysteine deprivation-induced ferroptosis of NSCLC cells in vitro and in vivo. Taken together, our data indicate the close association of COX7A1 with cysteine deprivation-induced ferroptosis, and provide a novel insight into the therapy mode against human NSCLC.

DOI: https://doi.org/10.1038/s41419-022-05430-3