Mitochondria-Shaping Proteins and Chemotherapy

Xie, Longlong; Zhou, Tiansheng; Xie, Yingchao; Bode, Ann M.; Cao, Yang

doi:10.3389/fonc.2021.769036

Cited by 12 publications

(8 citation statements)

References 128 publications

(158 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, our study suggests that co-treatment of platinum-based chemotherapies with CHK1 inhibitors, which restore SSBP1 localization to the mitochondria and increase ROS, may be an approach to overcome platinum resistance. Moreover, they suggest a general mechanism of resistance for therapeutic agents whose cytotoxicity is mediated in part by increasing the steady-state levels of nuclear H 2 O 2 and is in accordance with the growing body of evidence that mitochondrial function is a critical determinant of therapeutic response (Fu et al, 2021; Gentric et al, 2019; Shen et al, 2021; Xie et al, 2021).…”

Section: Discussionsupporting

confidence: 75%

Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway

Zhang

Simpson

Berner

et al. 2023

Preprint

View full text Add to dashboard Cite

Multiple chemotherapies are proposed to cause cell death in part by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs exactly how the resultant ROS function and are sensed is poorly understood. In particular, its unclear which proteins the ROS modify and their roles in chemotherapy sensitivity/resistance. To answer these questions, we examined 11 chemotherapies with an integrated proteogenomic approach identifying many unique targets for these drugs but also shared ones including ribosomal components, suggesting one mechanism by which chemotherapies regulate translation. We focus on CHK1 which we find is a nuclear H2O2 sensor that promotes an anti-ROS cellular program. CHK1 acts by phosphorylating the mitochondrial-DNA binding protein SSBP1, preventing its mitochondrial localization, which in turn decreases nuclear H2O2. Our results reveal a druggable nucleus-to-mitochondria ROS sensing pathway required to resolve nuclear H2O2 accumulation, which mediates resistance to platinum-based chemotherapies in ovarian cancers.

show abstract

Section: Discussionsupporting

confidence: 75%

Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway

Zhang

Simpson

Berner

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Finally, the upregulation of mitochondrial proteins involved both in ATP production and drug resistance [9], and/or immune-resistance [10] could lead to new therapies. In parallel, all these studies could also shed light on new biomarkers for better predictions of cancer chemosensitivity [11].…”

Section: Introductionmentioning

confidence: 93%

Long-Chain Acyl Coenzyme A Dehydrogenase, a Key Player in Metabolic Rewiring/Invasiveness in Experimental Tumors and Human Mesothelioma Cell Lines

Pouliquen,

Ortone,

Rumiano

et al. 2023

Cancers

View full text Add to dashboard Cite

Cross-species investigations of cancer invasiveness are a new approach that has already identified new biomarkers which are potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated with mitochondrial proteome rewiring. A comparison of significant abundance changes between invasive and non-invasive rat tumors gave a list of 433 proteins, including 26 proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines; the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs. epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

show abstract

“…OPA-1, along with Drp-1 play critical roles in preserving mitochondrial morphology and function. They are recognized as "mitochondria-shaping" proteins, responsible for mitochondria dynamic regulation through a careful balance between fission and fusion events [55]. Down-regulation of OPA-1, together with up-regulation of Drp-1, favor mitochondria fragmentation and cristae remodeling, facilitating the release of cytochrome c triggered by apoptotic stimuli [56,57].…”

Section: Plos Onementioning

confidence: 99%

Humic substances from composted fennel residues control the inflammation induced by Helicobacter pylori infection in AGS cells

Verrillo¹,

Cuomo²,

Montone³

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Helicobacter pylori (H. pylori) is a common human pathogen causing inflammation. Recent studies have suggested a sophisticated interplay between mitochondria, innate immunity and inflammatory response, thus proposing mitochondrial disfunction as the hallmark of severe inflammatory disorders. In this study, humic substances isolated from composted fennel residues (HS-FEN) were tested as potential therapeutical strategy to restore the mitochondrial physiology and control the inflammation associated with H. pylori infection. The molecular features of HS-FEN were characterized by infrared spectrometry, thermochemolysis-GC/MS, NMR spectroscopy, and high-performance size-exclusion chromatography (HPSEC), which revealed the presence of aromatic polyphenolic components arranged in a rather stable conformation. In vitro results showed antioxidant and anti-inflammatory properties of HS-FEN, that was found to increase the expression level of OPA-1 and SOD-2 genes and in AGS cells stimulated with H. pylori culture filtrate (Hpcf) and concomitantly decrease the expression level of Drp-1 gene and IL-12, IL-17 and G-CSF proteins. The hydrophobic features of HS, their conformational arrangement and large content of bioactive molecules may explain the beneficial effects of HS-FEN, that may potentially become an interesting source of anti-inflammatory agents capable to counteract or prevent the H. pylori-related inflammatory disorders.

show abstract

Mitochondria-Shaping Proteins and Chemotherapy

Cited by 12 publications

References 128 publications

Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway

Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway

Long-Chain Acyl Coenzyme A Dehydrogenase, a Key Player in Metabolic Rewiring/Invasiveness in Experimental Tumors and Human Mesothelioma Cell Lines

Humic substances from composted fennel residues control the inflammation induced by Helicobacter pylori infection in AGS cells

Contact Info

Product

Resources

About