Patricia Renard - Academia.edu (original) (raw)

Papers by Patricia Renard

Journal of Cellular and Molecular Medicine

PLOS ONE

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusi... more MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepato-cerebral mitochondrial DNA depletion syndrome in humans. In this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 does not control cancer cell proliferation despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines with two different shRNAs. However, shRNA-mediated MPV17 knockdown performed in this work provided misguiding results regarding the resulting proliferation phenotype and only a rescue experiment was able to shed definitive light on the implication of MPV17 in cancer cell proliferation. Our results therefore emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results.

Animals

Insect protein has the potential to become a sustainable feed ingredient for the rapidly growing ... more Insect protein has the potential to become a sustainable feed ingredient for the rapidly growing aquaculture industry. In the European Union, insect derived protein is placed under the same legislation as processed animal proteins (PAP). It is therefore of interest to develop methods for regulatory use, which unambiguously identify the species origin of insect-based ingredients. We performed (i) total protein quantification of insect samples using the traditional nitrogen-to-protein conversion factor of 6.25 and the sum of anhydrous amino acids, (ii) quantitative amino acid profiling and (iii) high-throughput tandem mass spectrometry to describe and differentiate 18 different commercial-grade insect meal samples derived from Hermetia illucens (8), Tenebrio molitor (5), Alphitobius diaperinus (3) and Acheta domesticus (2). In addition, we investigated and compared different protein extraction and digestion protocols for proteomic analysis. We found that irrespective of sample prepara...

Scientific Reports

Mitochondria are complex organelles that participate in many cellular functions, ranging from ATP... more Mitochondria are complex organelles that participate in many cellular functions, ranging from ATP production to immune responses against viruses and bacteria. This integration of a plethora of functions within a single organelle makes mitochondria a very attractive target to manipulate for intracellular pathogens. We characterised the crosstalk that exists between Brucella abortus, the causative agent of brucellosis, and the mitochondria of infected cells. Brucella replicates in a compartment derived from the endoplasmic reticulum (ER) and modulates ER functionality by activating the unfolded protein response. However, the impact of Brucella on the mitochondrial population of infected cells still requires a systematic study. We observed physical contacts between Brucella containing vacuoles and mitochondria. We also found that B. abortus replication is independent of mitochondrial oxidative phosphorylation and that mitochondrial reactive oxygen species do not participate to the control of B. abortus infection in vitro. We demonstrated that B. abortus and B. melitensis induce a drastic mitochondrial fragmentation at 48 hours post-infection in different cell types, including myeloid and non-myeloid cells. This fragmentation is DRP1-independent and might be caused by a deficit of mitochondrial fusion. However, mitochondrial fragmentation does not change neither Brucella replication efficiency, nor the susceptibility of infected cells to TNFα-induced apoptosis.

STEM CELLS

Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphory... more Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remains poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/b-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC-1a induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1a expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi-directional interactions control stem cell differentiation and mitochondrial abundance and activity. STEM CELLS 2017;35:2184-2197 SIGNIFICANCE STATEMENT Mitochondria, which represent the major source of energy and power for the cells, are increasingly recognized as major regulators of stem cells. In this study, we show that increasing the content and activity of mitochondria is essential for stem cell differentiation into hepatocytes. We identified a regulatory axis that couples the loss of pluripotency and commitment to differentiation to the increase of mitochondria abundance and activity. In turn, mitochondrial activity further supports the differentiation process. By better deciphering the interplay between mitochondria and stem cell differentiation, these findings could benefit the development of stemcell based therapeutics and regenerative medicine.

Journal of AOAC International, Jan 9, 2017

Food laboratories have developed methods for testing allergens in foods. The efficiency of qualit... more Food laboratories have developed methods for testing allergens in foods. The efficiency of qualitative and quantitativemethods is of prime importance in protecting allergic populations. Unfortunately, food laboratories encounter barriers to developing efficient methods. Bottlenecks include the lack of regulatory thresholds, delays in the emergence of reference materials and guidelines, and the need to detect processed allergens. In this study, ultra-HPLC coupled to tandem MS was used to illustrate difficulties encountered in determining method performances. We measured the major influences of both processing and matrix effects on the detection of egg, milk, soy, and peanut allergens in foodstuffs. The main goals of this work were to identify difficulties that food laboratories still encounter in detecting and quantifying allergens and to sensitize researchers to them.

Journal of cellular physiology, Jan 10, 2017

Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Variou... more Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial unc...

Cellular Immunology, 2016

Free radical biology & medicine, Oct 31, 2016

Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in can... more Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H2O2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation...

Nucleic Acids Research, 2016

HOX proteins define a family of key transcription factors regulating animal embryogenesis. HOX ge... more HOX proteins define a family of key transcription factors regulating animal embryogenesis. HOX genes have also been linked to oncogenesis and HOXA1 has been described to be active in several cancers, including breast cancer. Through a proteomewide interaction screening, we previously identified the TNFR-associated proteins RBCK1/HOIL-1 and TRAF2 as HOXA1 interactors suggesting that HOXA1 is functionally linked to the TNF/NF-B signaling pathway. Here, we reveal a strong positive correlation between expression of HOXA1 and of members of the TNF/NF-B pathway in breast tumor datasets. Functionally, we demonstrate that HOXA1 can activate NF-B and operates upstream of the NF-B inhibitor IB. Consistently, we next demonstrate that the HOXA1mediated activation of NF-B is non-transcriptional and that RBCK1 and TRAF2 influences on NF-B are epistatic to HOXA1. We also identify an 11 Histidine repeat and the homeodomain of HOXA1 to be required both for RBCK1 and TRAF2 interaction and NF-B stimulation. Finally, we highlight that activation of NF-B is crucial for HOXA1 oncogenic activity.

Comptes Rendus Des Seances De La Societe De Biologie Et De Ses Filiales, 1995

Journal of Cellular Physiology, 2015

Endoplasmic reticulum (ER) and mitochondria are not discrete intracellular organelles but establi... more Endoplasmic reticulum (ER) and mitochondria are not discrete intracellular organelles but establish close physical and functional interactions involved in several biological processes including mitochondrial bioenergetics, calcium homeostasis, lipid synthesis and the regulation of apoptotic cell death pathways. As many cell types might face a transient and sublethal ER stress during their lifetime, it is thus likely that the adaptive UPR response might affect the mitochondrial population. The aim of this work was to study the putative effects of a non-lethal and transient endoplasmic reticulum stress on the mitochondrial population in HepG2 cells. The results show that thapsigargin and brefeldin A, used to induce a transient and sublethal ER stress, rapidly lead to the fragmentation of the mitochondrial network associated with a decrease in mitochondrial membrane potential, O2 (•-) production and less efficient respiration. These changes in mitochondrial function are transient and preceeded by the phosphorylation of JNK. Inhibition of JNK activation by SP600125 prevents the decrease in O2 (•-) production and the mitochondrial network fragmentation observed in cells exposed to the ER stress but has no impact on the reduction of the mitochondrial membrane potential. In conclusion, our data shows that a non-lethal and transient ER stress triggers a rapid activation of JNK without inducing apoptosis, leading to the fragmentation of the mitochondrial network and a reduction of O2 (•-) production. This article is protected by copyright. All rights reserved.

International Journal of Molecular Sciences, 2015

Mitochondrial unfolded protein response is a form of retrograde signaling that contributes to ens... more Mitochondrial unfolded protein response is a form of retrograde signaling that contributes to ensuring the maintenance of quality control of mitochondria, allowing functional integrity of the mitochondrial proteome. When misfolded proteins or unassembled complexes accumulate beyond the folding capacity, it leads to alteration of proteostasis, damages, and organelle/cell dysfunction. Extensively studied for the ER, it was recently reported that this kind of signaling for mitochondrion would also be able to communicate with the nucleus in response to impaired proteostasis. The mitochondrial unfolded protein response (UPR mt) is activated in response to different types and levels of stress, especially in conditions where unfolded or misfolded mitochondrial proteins accumulate and aggregate. A specific UPR mt could thus be initiated to boost folding and degradation capacity in response to unfolded and aggregated protein accumulation. Although first described in mammals, the UPR mt was mainly studied in Caenorhabditis elegans, and accumulating evidence suggests that mechanisms triggered in response to a UPR mt might be different in C. elegans and mammals. In this review, we discuss and integrate recent data from the literature to address whether the UPR mt is relevant to mitochondrial homeostasis in mammals and to analyze the putative role of integrated stress response (ISR) activation in response to the inhibition of mtDNA expression and/or accumulation of mitochondrial mis/unfolded proteins.

Stem Cells and Development, 2015

As sites of cellular respiration and energy production, mitochondria play a central role in cell ... more As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. 2 WANET ET AL.

Mitochondrion, 2015

Mitochondria-to-nucleus communication, known as retrograde signaling, is important to adjust the ... more Mitochondria-to-nucleus communication, known as retrograde signaling, is important to adjust the nuclear gene expression in response to organelle dysfunction. Among the transcription factors described to respond to mitochondrial stress, CHOP-10 is activated by respiratory chain inhibition, mitochondrial accumulation of unfolded proteins and mtDNA mutations. In this study, we show that altered/impaired expression of mtDNA induces CHOP-10 expression in a signaling pathway that depends on the eIF2α/ATF4 axis of the integrated stress response rather than on the mitochondrial unfolded protein response.

Cell biology and toxicology, 1999

NFkappaB is a ubiquitous transcription factor involved in the proinflammatory response to cytokin... more NFkappaB is a ubiquitous transcription factor involved in the proinflammatory response to cytokines (such as IL-1 or TNF-alpha) and some particular stresses. The unraveling of the molecular mechanisms involved in its activation is quite recent, particularly in the case of IL-1-stimulated cells, but the identification of the molecules involved in this pathway opens new prospects in both pharmacological and toxicological research.