bims-mitpro 2024-03-10 papers

Issue of 2024–03–10
three papers selected by
Andreas Kohler, Umeå University

Nat Commun. 2024 Mar 04. 15(1): 1967

PsAF5 functions as an essential adapter for PsPHB2-mediated mitophagy under ROS stress in Phytophthora sojae.

Wenhao Li, Hongwei Zhu, Jinzhu Chen, Binglu Ru, Qin Peng, Jianqiang Miao, Xili Liu.

Host-derived reactive oxygen species (ROS) are an important defense means to protect against pathogens. Although mitochondria are the main intracellular targets of ROS, how pathogens regulate mitochondrial physiology in response to oxidative stress remains elusive. Prohibitin 2 (PHB2) is an inner mitochondrial membrane (IMM) protein, recognized as a mitophagy receptor in animals and fungi. Here, we find that an ANK and FYVE domain-containing protein PsAF5, is an adapter of PsPHB2, interacting with PsATG8 under ROS stress. Unlike animal PHB2 that can recruit ATG8 directly to mitochondria, PsPHB2 in Phytophthora sojae cannot recruit PsATG8 to stressed mitochondria without PsAF5. PsAF5 deletion impairs mitophagy under ROS stress and increases the pathogen's sensitivity to H2O2, resulting in the attenuation of P. sojae virulence. This discovery of a PsPHB2-PsATG8 adapter (PsAF5) in plant-pathogenic oomycetes reveals that mitophagy induction by IMM proteins is conserved in eukaryotes, but with differences in the details of ATG8 recruitment.

DOI: https://doi.org/10.1038/s41467-024-46290-z

Mol Cell Proteomics. 2024 Mar 04. pii: S1535-9476(24)00036-7. [Epub ahead of print] 100746

Ribosome Profiling and Mass Spectrometry Reveal Widespread Mitochondrial Translation Defects in a Striatal Cell Model of Huntington Disease.

Sunayana Dagar, Manish Sharma, George Tsaprailis, Catherina Scharager Tapia, Gogce Crynen, Preksha Sandipkumar Joshi, Neelam Shahani, Srinivasa Subramaniam.

Huntington disease (HD) is caused by an expanded polyglutamine mutation in huntingtin (mHTT) that promotes prominent atrophy in the striatum and subsequent psychiatric, cognitive, and choreiform movements. Multiple lines of evidence point to an association between HD and aberrant striatal mitochondrial functions; however, the present knowledge about whether (or how) mitochondrial mRNA translation is differentially regulated in HD remains unclear. We found that protein synthesis is diminished in HD mitochondria compared to healthy control striatal cell models. We utilized ribosome profiling (Ribo-Seq) to analyze detailed snapshots of ribosome occupancy of the mitochondrial mRNA transcripts in control and HD striatal cell models. The Ribo-Seq data revealed almost unaltered ribosome occupancy on the nuclear-encoded mitochondrial transcripts involved in oxidative phosphorylation (OXPHOS) (SDHA, Ndufv1, Timm23, Tomm5, Mrps22) in HD cells. By contrast, ribosome occupancy was dramatically increased for mitochondrially encoded OXPHOS mRNAs (mtNd-1, mtNd-2, mtNd-4, mtNd-4l, mtNd-5, mtNd-6, mt-Co1, mtCyt b, and mt-ATP8). We also applied tandem mass tag-based mass spectrometry (TMT-MS) identification of mitochondrial proteins to derive correlations between ribosome occupancy and actual mature mitochondrial protein products. We found many mitochondrial transcripts with comparable or higher ribosome occupancy, but diminished mitochondrial protein products, in HD. Thus, our study provides the first evidence of a widespread dichotomous effect on ribosome occupancy and protein turnover of mitochondria-related genes in HD.

Keywords: Dichotomy; abnormality; brain disease; cytoribosome; energy metabolism; mRNA translation; mitoribosome; oxidative stress; vulnerability

DOI: https://doi.org/10.1016/j.mcpro.2024.100746

J Cell Biol. 2024 Apr 01. pii: e202304075. [Epub ahead of print]223(4):

Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.

Jana Ovciarikova, Shikha Shikha, Alice Lacombe, Flavie Courjol, Rosalind McCrone, Wasim Hussain, Andrew Maclean, Leandro Lemgruber, Erica S Martins-Duarte, Mathieu Gissot, Lilach Sheiner.

Coordination between nucleus and mitochondria is essential for cell survival, and thus numerous communication routes have been established between these two organelles over eukaryotic cell evolution. One route for organelle communication is via membrane contact sites, functional appositions formed by molecular tethers. We describe a novel nuclear-mitochondrial membrane contact site in the protozoan Toxoplasma gondii. We have identified specific contacts occurring at the nuclear pore and demonstrated an interaction between components of the nuclear pore and the mitochondrial protein translocon, highlighting them as molecular tethers. Genetic disruption of the nuclear pore or the TOM translocon components, TgNup503 or TgTom40, respectively, result in contact site reduction, supporting their potential involvement in this tether. TgNup503 depletion further leads to specific mitochondrial morphology and functional defects, supporting a role for nuclear-mitochondrial contacts in mediating their communication. The discovery of a contact formed through interaction between two ancient mitochondrial and nuclear complexes sets the ground for better understanding of mitochondrial-nuclear crosstalk in eukaryotes.

DOI: https://doi.org/10.1083/jcb.202304075