Mitochondrial dysfunction promotes and aggravates the inflammatory response in normal human synoviocytes

Valcarcel‐Ares, Marta Noa; Riveiro-Naveira, Romina R.; Vaamonde‐García, Carlos; Loureiro, Jesús; Hermida-Carballo, L.; Blanco, Francisco J.; López-Armada, M.J.

doi:10.1093/rheumatology/keu016

Cited by 63 publications

(66 citation statements)

References 50 publications

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“…Recently, resveratrol that is a natural anti-inflammatory antioxidant has been reported to be a promising strategy in controlling synovial inflammatory response. 44 It supports our findings in this study.…”

Section: Discussionsupporting

confidence: 91%

Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients

et al. 2015

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Exome sequencings were conducted using 59 patients having rheumatoid arthritis (RA) and 93 controls. After stepwise filtering, 107 genes showed less than 0.05 of P-values by gene-burden tests. Among 107 genes, NDUFA7 which is a subunit of the complex I in the mitochondrial respiratory chain was selected for further analysis based on previous reports. A case-control study was performed on the three single-nucleotide variants (SNVs) of NDUFA7 with 432 cases and 432 controls. An association was observed between NDUFA7 and RA with severe erosive arthritis. These results together with previous reports suggested the involvement of reactive oxygen species (ROS) in the pathogenesis of RA. In the next step, four SNVs from three genes related to the mitochondrial respiratory chain were selected, which is a major source of ROS, and conducted a case-control study. An association was observed based on a pathway-burden test comprising NDUFA7, SDHAF2, SCO1 and ATP5O: P=1.56E-04, odds ratio=2.16, 95% confidence interval=1.43-3.28. Previous reports suggested the involvement of ROS in the pathogenesis of RA. The aggregation of SNVs in the mitochondria respiratory chain suggests the pivotal role of those SNVs in the pathogenesis of RA with severe erosive arthritis.

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Section: Discussionsupporting

confidence: 91%

Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients

et al. 2015

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“…Furthermore, as part of its proinflammatory effect, TNF- α promotes ROS production [61]. Mitochondrial dysfunction increases inflammatory responses in normal human synoviocytes, and these are ameliorated by antioxidants, including mitoTEMPO, N-acetylcysteine, and resveratrol [62]. Mitochondria also have multiple roles in cardiac pathophysiology.…”

Section: Cellular Organelle-mediated Inflammationmentioning

confidence: 99%

Role of Mitochondria-Associated Endoplasmic Reticulum Membrane in Inflammation-Mediated Metabolic Diseases

Thoudam

Jeon

et al. 2016

Mediators of Inflammation

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Inflammation is considered to be one of the most critical factors involved in the development of complex metabolic diseases such as type 2 diabetes, cancer, and cardiovascular disease. A few decades ago, the discovery of mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) was followed by the identification of its roles in regulating cellular homeostatic processes, ranging from cellular bioenergetics to apoptosis. MAM provides an excellent platform for numerous signaling pathways; among them, inflammatory signaling pathways associated with MAM play a critical role in cellular defense during pathogenic infections and metabolic disorders. However, induction of MAM causes deleterious effects by amplifying mitochondrial reactive oxygen species generation through increased calcium transfer from the ER to mitochondria, thereby causing mitochondrial damage and release of mitochondrial components into the cytosol as damage-associated molecular patterns (DAMPs). These mitochondrial DAMPs rapidly activate MAM-resident inflammasome components and other inflammatory factors, which promote inflammasome complex formation and release of proinflammatory cytokines in pathological conditions. Long-term stimulation of the inflammasome instigates chronic inflammation, leading to the pathogenesis of metabolic diseases. In this review, we summarize the current understanding of MAM and its association with inflammation-mediated metabolic diseases.

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“…Currently available data suggest involvement of TNF-α, and TNF-α-associated ROS generation in induction of mtDNA mutations [177, 178]. Mitochondrial dysfunction as a result of compromised metabolism induced by the ATP synthase inhibitor oligomycin, has been shown to promote ROS- and NF-κB-dependent induction of inflammatory markers by normal human synoviocytes [179]. …”

Section: The Nine Hallmarks Of Aging and Ramentioning

confidence: 99%

Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging

Chalan¹,

Berg²,

Kroesen

et al. 2015

CAS

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Age is the most important risk factor for the development of infectious diseases, cancer and chronic inflammatory diseases including rheumatoid arthritis (RA). The very act of living causes damage to cells. A network of molecular, cellular and physiological maintenance and repair systems creates a buffering capacity against these damages. Aging leads to progressive shrinkage of the buffering capacity and increases vulnerability. In order to better understand the complex mammalian aging processes, nine hallmarks of aging and their interrelatedness were recently put forward.RA is a chronic autoimmune disease affecting the joints. Although RA may develop at a young age, the incidence of RA increases with age. It has been suggested that RA may develop as a consequence of premature aging (immunosenescence) of the immune system. Alternatively, premature aging may be the consequence of the inflammatory state in RA. In an effort to answer this chicken and egg conundrum, we here outline and discuss the nine hallmarks of aging, their contribution to the pre-aged phenotype and the effects of treatment on the reversibility of immunosenescence in RA.

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Mitochondrial dysfunction promotes and aggravates the inflammatory response in normal human synoviocytes

Cited by 63 publications

References 50 publications

Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients

Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients

Role of Mitochondria-Associated Endoplasmic Reticulum Membrane in Inflammation-Mediated Metabolic Diseases

Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging

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