bims-cytox1 2023-02-05 papers

Issue of 2023‒02‒05
four papers selected by
Gavin McStay
Liverpool John Moores University

Plant Physiol. 2023 Feb 01. pii: kiad062. [Epub ahead of print]

Tetratricopeptide-containing SMK11 is essential for the assembly of cytochrome c oxidase in maize mitochondria.

Zhenjing Ren, Kaijian Fan, Sihan Zhen, Jie Zhang, Yan Liu, Junjie Fu, Chunlai Qi, Qianhan Wei, Yao Du, Wurinile Tatar, Xiaofeng Zhang, Guoying Wang, Allan G Rasmusson, Jianhua Wang, Yunjun Liu.

Assembly of the functional complexes of the mitochondrial respiratory chain requires sophisticated and efficient regulatory mechanisms. In plants, the subunit composition and assembly factors involved in the biogenesis of cytochrome c oxidase (complex IV) are substantially less defined than in mammals and yeast. In this study, we cloned maize (Zea mays) Small kernel 11 (Smk11) via map-based cloning. Smk11 encodes a mitochondria-localized tetratricopeptide repeat (TPR) protein. Disruption of Smk11 severely affected the assembly and activity of mitochondrial complex IV, leading to delayed plant growth and seed development. Protein interactions studies revealed that SMK11 might interact with four putative complex IV assembly factors, Inner membrane peptidase 1A (ZmIMP1A), MYB domain protein 3R3 (ZmMYB3R-3), Cytochrome c oxidase 23 (ZmCOX23), and Mitochondrial ferredoxin 1 (ZmMFDX1), among which ZmMFDX1 might interact with subunits ZmCOX6a and ZmCOX-X1; ZmMYB3R-3 might also interact with ZmCOX6a. The mutation of SMK11 perturbed the normal assembly of these subunits, leading to the inactivation of complex IV. The results of this study revealed that SMK11 serves as an accessory assembly factor required for the normal assembly of subunits into complex IV, which will accelerate the elucidation of the assembly of complex IV in plant mitochondria.

Keywords: Smk11 ; assembly factor; cytochrome c oxidase; kernel development; maize

DOI: https://doi.org/10.1093/plphys/kiad062

Bioessays. 2023 Jan 29. e2200160

Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond.

Eirini Lionaki, Ilias Gkikas, Nektarios Tavernarakis.

Mitochondria hold diverse and pivotal roles in fundamental processes that govern cell survival, differentiation, and death, in addition to organismal growth, maintenance, and aging. The mitochondrial protein import system is a major contributor to mitochondrial biogenesis and lies at the crossroads between mitochondrial and cellular homeostasis. Recent findings highlight the mitochondrial protein import system as a signaling hub, receiving inputs from other cellular compartments and adjusting its function accordingly. Impairment of protein import, in a physiological, or disease context, elicits adaptive responses inside and outside mitochondria. In this review, we discuss recent developments, relevant to the mechanisms of mitochondrial protein import regulation, with a particular focus on quality control, proteostatic and metabolic cellular responses, triggered upon impairment of mitochondrial protein import.

Keywords: metabolism; mitochondrial protein import; mitochondrial unfolded protein response; mitophagy; proteostasis

DOI: https://doi.org/10.1002/bies.202200160

Biochim Biophys Acta Bioenerg. 2023 Jan 25. pii: S0005-2728(23)00002-6. [Epub ahead of print]1864(2): 148956

Calcium-bound structure of bovine cytochrome c oxidase.

Kazumasa Muramoto, Kyoko Shinzawa-Itoh.

The crystal structure of bovine cytochrome c oxidase (CcO) shows a sodium ion (Na+) bound to the surface of subunit I. Changes in the absorption spectrum of heme a caused by calcium ions (Ca2+) are detected as small red shifts, and inhibition of enzymatic activity under low turnover conditions is observed by addition of Ca2+ in a competitive manner with Na+. In this study, we determined the crystal structure of Ca2+-bound bovine CcO in the oxidized and reduced states at 1.7 Å resolution. Although Ca2+ and Na+ bound to the same site of oxidized and reduced CcO, they led to different coordination geometries. Replacement of Na+ with Ca2+ caused a small structural change in the loop segments near the heme a propionate and formyl groups, resulting in spectral changes in heme a. Redox-coupled structural changes observed in the Ca2+-bound form were the same as those previously observed in the Na+-bound form, suggesting that binding of Ca2+ does not severely affect enzymatic function, which depends on these structural changes. The relation between the Ca2+ binding and the inhibitory effect during slow turnover, as well as the possible role of bound Ca2+ are discussed.

Keywords: Calcium ion; Cytochrome c oxidase; X-ray crystallography

DOI: https://doi.org/10.1016/j.bbabio.2023.148956

bioRxiv. 2023 Jan 19. pii: 2023.01.19.524708. [Epub ahead of print]

Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins.

Rosario Avolio, Ilenia Agliarulo, Daniela Criscuolo, Daniela Sarnataro, Margherita Auriemma, Sara Pennacchio, Giovanni Calice, Martin Y Ng, Carlotta Giorgi, Paolo Pinton, Barry Cooperman, Matteo Landriscina, Franca Esposito, Danilo Swann Matassa.

A complex interplay between mRNA translation and cellular respiration has been recently unveiled, but its regulation in humans is poorly characterized in either health or disease. Cancer cells radically reshape both biosynthetic and bioenergetic pathways to sustain their aberrant growth rates. In this regard, we have shown that the molecular chaperone TRAP1 not only regulates the activity of respiratory complexes, behaving alternatively as an oncogene or a tumor suppressor, but also plays a concomitant moonlighting function in mRNA translation regulation. Herein we identify the molecular mechanisms involved, demonstrating that TRAP1: i) binds both mitochondrial and cytosolic ribosomes as well as translation elongation factors, ii) slows down translation elongation rate, and iii) favors localized translation in the proximity of mitochondria. We also provide evidence that TRAP1 is coexpressed in human tissues with the mitochondrial translational machinery, which is responsible for the synthesis of respiratory complex proteins. Altogether, our results show an unprecedented level of complexity in the regulation of cancer cell metabolism, strongly suggesting the existence of a tight feedback loop between protein synthesis and energy metabolism, based on the demonstration that a single molecular chaperone plays a role in both mitochondrial and cytosolic translation, as well as in mitochondrial respiration.

DOI: https://doi.org/10.1101/2023.01.19.524708