bims-resufa 2024-09-01 papers

Issue of 2024‒09‒01
two papers selected by
Gavin McStay, Liverpool John Moores University

Plant Cell. 2024 Aug 23. pii: koae242. [Epub ahead of print]

EARLY NODULIN93 acts via cytochrome c oxidase to alter respiratory ATP production and root growth in plants.

Chun Pong Lee, Xuyen H Le, Ryan M R Gawryluk, José A Casaretto, Steven J Rothstein, A Harvey Millar.

EARLY NODULIN 93 (ENOD93) has been genetically associated with biological nitrogen fixation in legumes and nitrogen use efficiency in cereals, but its precise function is unknown. We show that hidden Markov models define ENOD93 as a homolog of the N-terminal domain of RESPIRATORY SUPERCOMPLEX FACTOR 2 (RCF2). RCF2 regulates cytochrome oxidase (CIV), influencing the generation of a mitochondrial proton motive force in yeast (Saccharomyces cerevisiae). Knockout of ENOD93 in Arabidopsis (Arabidopsis thaliana) causes a short root phenotype and early flowering. ENOD93 is associated with a protein complex the size of CIV in mitochondria, but neither CIV abundance nor its activity changed in ruptured organelles of enod93. However, a progressive loss of ADP-dependent respiration rate was observed in intact enod93 mitochondria, which could be recovered in complemented lines. Mitochondrial membrane potential was higher in enod93 in a CIV-dependent manner, but ATP synthesis and ADP depletion rates progressively decreased. The respiration rate of whole enod93 seedlings was elevated, and root ADP content was nearly double that in wild type without a change in ATP content. We propose that ENOD93 and HYPOXIA-INDUCED GENE DOMAIN 2 (HIGD2) are the functional equivalent of yeast RCF2 but have remained undiscovered in many eukaryotic lineages because they are encoded by two distinct genes.

Keywords: ATP synthesis; Complex IV; Early nodulin 93; RCF2; mitochondrial oxidative phosphorylation

DOI: https://doi.org/10.1093/plcell/koae242

Sci Rep. 2024 08 24. 14(1): 19673

Detailed analysis of Mdivi-1 effects on complex I and respiratory supercomplex assembly.

Nico Marx, Nadine Ritter, Paul Disse, Guiscard Seebohm, Karin B Busch.

Several human diseases, including cancer and neurodegeneration, are associated with excessive mitochondrial fragmentation. In this context, mitochondrial division inhibitor (Mdivi-1) has been tested as a therapeutic to block the fission-related protein dynamin-like protein-1 (Drp1). Recent studies suggest that Mdivi-1 interferes with mitochondrial bioenergetics and complex I function. Here we show that the molecular mechanism of Mdivi-1 is based on inhibition of complex I at the IQ site. This leads to the destabilization of complex I, impairs the assembly of N- and Q-respirasomes, and is associated with increased ROS production and reduced efficiency of ATP generation. Second, the calcium homeostasis of cells is impaired, which for example affects the electrical activity of neurons. Given the results presented here, a potential therapeutic application of Mdivi-1 is challenging because of its potential impact on synaptic activity. Similar to the Complex I inhibitor rotenone, Mdivi-1 may lead to neurodegenerative effects in the long term.

Keywords: Calcium metabolism; Inhibition; Mdivi-1; Mitochondria; Neuronal activity; Respiratory complex I; Respiratory supercomplexes

DOI: https://doi.org/10.1038/s41598-024-69748-y