Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren’s syndrome

Barrera, María-José; Aguilera, Sergio; Castro, Iná Elias de; Carvajal, Patricia; Jara, Daniela; Molina, Claudio; González, Sergio; González, María-Julieta

doi:10.1016/j.autrev.2021.102867

Cited by 121 publications

(92 citation statements)

References 171 publications

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“…Mitochondrial fusion is usually protective, and mitochondrial fission is crucial to clearing the damaged mitochondria by mitophagy. Repeated cycles of fusion and fission facilitate the sharing of mitochondrial genetic content, ions, metabolites, and proteins ( 14 ). Therefore, to probe the relationship between mitochondrial dynamics and the immune microenvironment in pSS was warranted.…”

Section: Resultsmentioning

confidence: 99%

“…DAMPs are known as intracellular components such as endogenous proteins released from dying or dead cells during inflammation. When salivary gland tissue is damaged, DAMPs might be increasingly formed or released from epithelial cells, and the elevated extracellular DAMPs could recruit and activate immune cells ( 14 ). The transcriptional analysis revealed that the mRNA levels of NLRP3 , ZBP1 , TNF , and IL-1β were upregulated with increased lymphocyte infiltration ( Figure 6A ), which could be negatively related to mitochondria gluconeogenesis, ketone metabolism, and lipid metabolism in pSS ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

“…In particular, the glandular inflammatory activity in pSS appears to be increasing linearly higher for IL-6 and IL-17 levels ( 10 , 13 ). Although the exact mechanisms underlying the creation of such an inflammatory environment remain poorly understood, chronic inflammatory conditions might be activated by the disruption of cellular homeostasis, in addition to infection and injury ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…suggested that release of molecular danger signals from damaged ROS-generating mitochondria triggered a potent inflammatory response via pattern recognition receptors (PRRs). Further, alterations with mitochondria-endoplasmic reticulum contact sites could increase inflammatory signaling ( 14 ). In addition, our previous study first reported alterations in the ultrastructure of cellular organelles in both acini and ducts from minor salivary glands, including swelling of mitochondria, and associated with disease severity ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome

et al. 2022

Front. Immunol.

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BackgroundPrimary Sjogren’s syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown.MethodsThe mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease.ResultsThe bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38, CMPK2, TBC1D9, and PYCR1, were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1, DRP1, and MFF) and fusion (MFN1, MFN2, and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells.ConclusionOur study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome

et al. 2022

Front. Immunol.

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“…Mitochondria are the main source of ATP and ROS, as well as a key organelle for maintaining cellular homeostasis. Mitochondrial dysfunction increase the production of ROS and further induce inflammation (Barrera et al., 2021 ). Mitochondria are the main target of flavonoids (Lagoa et al., 2011 ).…”

Section: Resultsmentioning

confidence: 99%

Anti‐inflammatory activity of cyanidin‐3‐O‐glucoside and cyanidin‐3‐O‐glucoside liposomes in THP‐1 macrophages

Hao

Guan

Huang

et al. 2021

Food Science & Nutrition

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Inflammation is a response of the body to stimulation, which may be beneficial or harmful. Inflammation may either be acute or chronic, and is related to the homeostasis of physiological systems in vivo. Inflammation is associated with many diseases and is the basis of most pathological processes. The main causes of inflammation are infection and tissue damage, which can lead to the concentration of leukocytes and plasma proteins (Medzhitov, 2008).Chronic inflammation is involved in many diseases, including diabetes, obesity, atherosclerosis, and cancer (Coussens & Werb, 2002;

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Redox Pathogenesis in Rheumatic Diseases

Laniak,

Winans,

Patel

et al. 2024

ACR Open Rheumatology

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Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions.

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Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren’s syndrome

Cited by 121 publications

References 171 publications

A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome

A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome

Anti‐inflammatory activity of cyanidin‐3‐O‐glucoside and cyanidin‐3‐O‐glucoside liposomes in THP‐1 macrophages

Redox Pathogenesis in Rheumatic Diseases

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