bims-cytox1 2024-03-31 papers

Issue of 2024‒03‒31
four papers selected by
Gavin McStay, Liverpool John Moores University

Biochem Soc Trans. 2024 Mar 25. pii: BST20231183. [Epub ahead of print]

Emerging mechanisms in the redox regulation of mitochondrial cytochrome c oxidase assembly and function.

Suleva Povea-Cabello, Michele Brischigliaro, Erika Fernández-Vizarra.

In eukaryotic cells, mitochondria perform cellular respiration through a series of redox reactions ultimately reducing molecular oxygen to water. The system responsible for this process is the respiratory chain or electron transport system (ETS) composed of complexes I-IV. Due to its function, the ETS is the main source of reactive oxygen species (ROS), generating them on both sides of the mitochondrial inner membrane, i.e. the intermembrane space (IMS) and the matrix. A correct balance between ROS generation and scavenging is important for keeping the cellular redox homeostasis and other important aspects of cellular physiology. However, ROS generated in the mitochondria are important signaling molecules regulating mitochondrial biogenesis and function. The IMS contains a large number of redox sensing proteins, containing specific Cys-rich domains, that are involved in ETS complex biogenesis. The large majority of these proteins function as cytochrome c oxidase (COX) assembly factors, mainly for the handling of copper ions necessary for the formation of the redox reactive catalytic centers. A particular case of ROS-regulated COX assembly factor is COA8, whose intramitochondrial levels are increased by oxidative stress, promoting COX assembly and/or protecting the enzyme from oxidative damage. In this review, we will discuss the current knowledge concerning the role played by ROS in regulating mitochondrial activity and biogenesis, focusing on the COX enzyme and with a special emphasis on the functional role exerted by the redox sensitive Cys residues contained in the COX assembly factors.

Keywords: complex IV; mitochondrial dysfunction; reactive oxygen species; redox signaling; respiratory chain assembly

DOI: https://doi.org/10.1042/BST20231183

IUBMB Life. 2024 Mar 26.

Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae.

Mazzen H Eldeeb, Lizeth J Camacho Lopez, Flavia Fontanesi.

The functional and structural relationship among the individual components of the mitochondrial respiratory chain constitutes a central aspect of our understanding of aerobic catabolism. This interplay has been a subject of intense debate for over 50 years. It is well established that individual respiratory enzymes associate into higher-order structures known as respiratory supercomplexes, which represent the evolutionarily conserved organizing principle of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, supercomplexes are formed by a complex III homodimer flanked by one or two complex IV monomers, and their high-resolution structures have been recently elucidated. Despite the wealth of structural information, several proposed supercomplex functions remain speculative and our understanding of their physiological relevance is still limited. Recent advances in the field were made possible by the construction of yeast strains where the association of complex III and IV into supercomplexes is impeded, leading to diminished respiratory capacity and compromised cellular competitive fitness. Here, we discuss the experimental evidence and hypotheses relative to the functional roles of yeast respiratory supercomplexes. Moreover, we review the current models of yeast complex III and IV assembly in the context of supercomplex formation and highlight the data scattered throughout the literature suggesting the existence of cross talk between their biogenetic processes.

Keywords: III2IV1; III2IV2; OXPHOS biogenesis; Saccharomyces cerevisiae; cellular respiratory capacity; mitochondrial respiratory supercomplexes

DOI: https://doi.org/10.1002/iub.2817

J Cell Biol. 2024 May 06. pii: e202306051. [Epub ahead of print]223(5):

OMA1 protease eliminates arrested protein import intermediates upon mitochondrial depolarization.

Magda Krakowczyk, Anna M Lenkiewicz, Tomasz Sitarz, Dominika Malinska, Mayra Borrero, Ben Hur Marins Mussulini, Vanessa Linke, Andrzej A Szczepankiewicz, Joanna M Biazik, Agata Wydrych, Hanna Nieznanska, Remigiusz A Serwa, Agnieszka Chacinska, Piotr Bragoszewski.

Most mitochondrial proteins originate from the cytosol and require transport into the organelle. Such precursor proteins must be unfolded to pass through translocation channels in mitochondrial membranes. Misfolding of transported proteins can result in their arrest and translocation failure. Arrested proteins block further import, disturbing mitochondrial functions and cellular proteostasis. Cellular responses to translocation failure have been defined in yeast. We developed the cell line-based translocase clogging model to discover molecular mechanisms that resolve failed import events in humans. The mechanism we uncover differs significantly from these described in fungi, where ATPase-driven extraction of blocked protein is directly coupled with proteasomal processing. We found human cells to rely primarily on mitochondrial factors to clear translocation channel blockage. The mitochondrial membrane depolarization triggered proteolytic cleavage of the stalled protein, which involved mitochondrial protease OMA1. The cleavage allowed releasing the protein fragment that blocked the translocase. The released fragment was further cleared in the cytosol by VCP/p97 and the proteasome.

DOI: https://doi.org/10.1083/jcb.202306051

Int J Mol Sci. 2024 Mar 21. pii: 3542. [Epub ahead of print]25(6):

PPR596 Is Required for nad2 Intron Splicing and Complex I Biogenesis in Arabidopsis.

Aqib Sayyed, Baoyin Chen, Yong Wang, Shi-Kai Cao, Bao-Cai Tan.

Mitochondria are essential organelles that generate energy via oxidative phosphorylation. Plant mitochondrial genome encodes some of the respiratory complex subunits, and these transcripts require accurate processing, including C-to-U RNA editing and intron splicing. Pentatricopeptide repeats (PPR) proteins are involved in various organellar RNA processing events. PPR596, a P-type PPR protein, was previously identified to function in the C-to-U editing of mitochondrial rps3 transcripts in Arabidopsis. Here, we demonstrate that PPR596 functions in the cis-splicing of nad2 intron 3 in mitochondria. Loss of the PPR596 function affects the editing at rps3eU1344SS, impairs nad2 intron 3 splicing and reduces the mitochondrial complex I's assembly and activity, while inducing alternative oxidase (AOX) gene expression. This defect in nad2 intron splicing provides a plausible explanation for the slow growth of the ppr595 mutants. Although a few P-type PPR proteins are involved in RNA C-to-U editing, our results suggest that the primary function of PPR596 is intron splicing.

Keywords: Arabidopsis; C-to-U RNA editing; PPR596; complex I assembly; mitochondrial respiratory chain; nad2 intron splicing

DOI: https://doi.org/10.3390/ijms25063542