An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicity

Miallot, Richard; Millet, Virginie; Groult, Yann; Modelska, A.; Crescence, Lydie; Roulland, Sandrine; Henri, Sandrine; Malissen, Bernard; Brouilly, Nicolas; Panicot‐Dubois, Laurence; Vincentelli, Renaud; Sulzenbacher, G.; Finetti, Pascal; Dutour, Aurélie; Blay, Jean‐Yves; Bertucci, François; Galland, Franck; Naquet, Philippe

doi:10.26508/lsa.202201767

Cited by 5 publications

(4 citation statements)

References 70 publications

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“…Conversely, in human bone sarcomas, VNN1 expression does not correlate with prognosis, and Pant does not control tumor growth in mice. This phenotype may be related to the fact that loss of mtDNA is often found associated with aggressive osteosarcomas ( Jackson et al, 2019 ), whereas its enhanced release can boost cDC1-dependent immune responses in MCA tumors ( Miallot et al, 2023a ). Such in silico analyses display strengths and limitations.…”

Section: Discussionmentioning

confidence: 99%

The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

Miallot,

Millet,

Roger

et al. 2023

Life Sci. Alliance

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The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8+T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans,VNN1expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity.

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Section: Discussionmentioning

confidence: 99%

The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

Miallot,

Millet,

Roger

et al. 2023

Life Sci. Alliance

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“…Hence, the tumor microenvironment with high oxidative stress levels may explain the up-regulation of YME1L and downregulation of OMA1. Moreover, it is reported that downregulation of OMA1 may be responsible for increased ROS production [43].…”

Section: The Assessment Of the Hepatic Metastatic Markersmentioning

confidence: 99%

OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma

Abass,

Abdel-Hamid,

Elshazly

et al. 2023

Yale J Biol Med

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Identifying new hepatocellular carcinoma (HCC)-driven signaling molecules and discovering their molecular mechanisms are crucial for efficient and better outcomes. Recently, OMA1 and YME1L, the inner mitochondrial proteases, were displayed to be associated with tumor progression in various cancers; however, their role in HCC has not yet been studied. Therefore, we evaluated the possible role of OMA1/ YME1L in HCC staging and discussed their potential role in cellular apoptosis and proliferation. Our study was performed using four groups of male albino rats: a normal control and three diethyl nitrosaminetreated groups for 8, 16, and 24 weeks. The OMA1 and YME1L, matrix-metalloproteinase-9 (MMP-9), and cyclin D1 content were measured in liver tissues, while alpha-fetoprotein (AFP) level was assessed in serum. Additionally, Ki-67 expression was evaluated by immunohistochemistry. The relative hepatic expression of Bax, and tissue inhibitor matrix metalloproteinase (TIMP-3) was measured. Herein, we confirmed for the first time that OMA1 is down-regulated while YME1L is up-regulated in HCC in the three studied stages with subsequent inhibition of apoptosis and cell cycle progression. Furthermore, these proteases have a possible role in metastasis. These newly recognized results suggested OMA1 and YME1L as possible diagnostic tools and therapeutic targets for HCC management.

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“…OMA1 is a zinc‐dependent protein in the inner mitochondrial membrane 15 . Fascinatingly, separate areas of the OMA1 , such as metallo‐endopeptidase protein participate in stress sensing 19 . In normal conditions, the presence of OMA1 leads to the establishment of homeostasis between fusion and fission.…”

Section: Introductionmentioning

confidence: 99%

“…15 Fascinatingly, separate areas of the OMA1, such as metallo-endopeptidase protein participate in stress sensing. 19 In normal conditions, the presence of OMA1 leads to the establishment of homeostasis between fusion and fission. Upon mitochondrial depolarization or oxidative stress, OMA1 cleavage of some goal proteins, such as OPA1 (optic atrophy 1) leads to the dominance of fission and mitochondrial fragmentation.…”

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confidence: 99%

Peripheral blood mononuclear cells show markers of mitochondrial dysfunction in rheumatoid arthritis

Abbasifard,

Solgi,

Khodadadi

et al. 2024

Cell Biochemistry & Function

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Metabolic and mitochondrial dysregulation are critical causal factors in the pathogenesis and progression of RA. Mitochondrial dysfunction include abnormal energy metabolism, and excessive production of reactive oxygen species (ROS). This study aimed to investigate the adenosine triphosphate (ATP), mitochondrial membrane potential (ΔΨm), ROS, and mRNA expression level of ROMO1 (as ROS modulator) and OMA1 (as regulator mitochondrial dynamics) of peripheral blood mononuclear cells (PBMC) in RA patients. The study participants were 50 patients with RA and 50 sex‐ and age‐matched healthy volunteers. PBMC of all participant were isolated by Ficoll‐Paque. Alteration in ΔΨm and cellular ROS were measured using flow cytometry, ATP level was also assessed via luminometry, and ROMO1 and OMA1 mRNA expression via qRT‐PCR assay. A significant decrease in ATP (p = .005) and ΔΨm (p < .001) was observed in the PBMC of RA compared to control. The ROS levels were significantly higher in the PBMC of RA compared to the control (p < .001). ROMO1 and OMA1 mRNA expression was also significantly increased in RA patients compared to control (p < .001). The decrease in ATP is strongly associated with ROS increasing in PBMC of RA patients, denoting an inverse and negative relationship between ATP and ROS production. Also, a decrease in ΔΨm was observed. It seems that in line with mitochondrial dysfunction in PBMC, increased expression of ROMO1 and OMA1 genes could also be involved in the development of RA.

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An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicity

Cited by 5 publications

References 70 publications

The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma

Peripheral blood mononuclear cells show markers of mitochondrial dysfunction in rheumatoid arthritis

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