Biology subjects

Arnould, T.

Publications and source records attributed to Arnould, T..

3 recordsLinked to original sources

bioRxiv2024

In-depth study of MPV17: a molecular travel unveiling a mitochondrial calcium regulation function

Mitochondrial DNA depletion syndromes are severe genetic disorders associated with mutations in a variety of genes including MPV17, encoding a protein of the inner mitochondrial membrane with an unclear function. In this study, using BioID technology, we identified MPV17 interacting partners among which proteins from the MICOS complex. However, MPV17 knockout did not impact mitochondrial ultrastructure, but led to increased mitochondria-derived vesicles formation and altered mitochondrial permeability transition pore. Furthermore, MPV17 KO cells exhibited higher mitochondrial calcium levels and reactive oxygen species, leading to mtDNA degradation, a phenomenon prevented by blocking mitochondrial calcium entry or treating cells with antioxidant. We thus propose a function for MPV17 as a potential additional member of the mitochondrial permeability transition pore, whereas in the absence of the protein, the build-up of calcium inside the mitochondria would lead to mtDNA degradation caused by increased oxidative damages.

cell biology↗

bioRxiv2022

BNIP3L-mediated mitophagy triggered by Brucella in host cells is required for bacterial egress

The facultative intracellular pathogen Brucella abortus interacts with several organelles of the host cell to reach its replicative niche inside the endoplasmic reticulum. However, little is known about the interplay between the bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers a strong mitochondrial network fragmentation accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles in the late steps of cellular infection. The expression of the mitophagy receptor BNIP3L induced by B. abortus is essential for these events and relies on the iron-dependent stabilization of the hypoxia-inducible factor 1 alpha. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit of the host cell as BNIP3L depletion drastically reduced the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.

microbiology↗

bioRxiv2022

A critical role for heme synthesis and succinate in the regulation of pluripotent states transitions

Using embryonic stem cells (ESCs) in regenerative medicine or in disease modeling requires a complete understanding of these cells. Two main distinct developmental states of ESCs have been stabilized in vitro, a naive pre-implantation stage and a primed post-implantation stage. Based on two recently published CRISPR-Cas9 knockout functional screens, we show here that the exit of the naive state is impaired upon heme biosynthesis pathway blockade, linked to the incapacity to activate MAPK- and TGF{beta}-dependent signaling pathways. In addition, heme synthesis inhibition promotes the acquisition of 2 cell-like cells in a heme-independent manner caused by a mitochondrial succinate accumulation and leakage out of the cell. We further demonstrate that extra-cellular succinate acts as a paracrine/autocrine signal, able to trigger the 2C-like reprogramming through the activation of its plasma membrane receptor, SUCNR1. Overall, this study unveils a new mechanism underlying the maintenance of pluripotency under the control of heme synthesis.

developmental biology↗