The Role of Mitochondria in Systemic Lupus Erythematosus: A Glimpse of Various Pathogenetic Mechanisms

Abstract

Background: Systemic Lupus Erythematosus (SLE) is a polysystem autoimmune disease that adversely affects human health. Various organs can be affected, including the kidney or brain. Traditional treatment methods for SLE primarily rely on glucocorticoids and immunosuppressors. Unfortunately, these therapeutic agents cannot prevent a high recurrence rate after SLE remission. Therefore, novel therapeutic targets are urgently required. Methods: A systematic search of the published literature regarding the abnormal structure and function of mitochondria in SLE and therapies targeting mitochondria was performed in several databases. Results: Accumulating evidence indicates that mitochondrial dysfunction plays important roles in the pathogenesis of SLE, including influencing mitochondrial DNA damage, mitochondrial dynamics change, abnormal mitochondrial biogenesis and energy metabolism, mitophagy, oxidative stress, inflammatory reactions, apoptosis and NETosis. Further investigation of mitochondrial pathophysiological roles will result in further clarification of SLE. Specific lupus-induced organ damage also exhibits characteristic mitochondrial changes. Conclusion: This review aimed to summarize the current research on the role of mitochondrial dysfunction in SLE, which will necessarily provide potential novel therapeutic targets for SLE.

Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lprmice

“…IntROduCtIOn SLE is a complex and heterogeneous autoimmune syndrome characterised by numerous abnormalities, including various autoantibodies, the appearance of unusual CD4-CD8-TCR-αβ + cells, altered metabolism of lymphocytes, a type I interferon (IFN-I) gene signature in peripheral blood mononuclear cells (PBMC), increased formation of neutrophil extracellular traps (NETs), and deposition of immunoglobulins and complement at renal glomeruli. [1][2][3][4][5][6][7][8][9][10] Each of these immune abnormalities may provoke different aspects of the disease, and each also may be driven by different environmental and genetic aberrations. Recent work has also revealed the importance of non-immune factors, such as oxidative stress, in the development of endorgan damage in SLE, shifting the paradigm of SLE pathogenesis from that of a disease provoked solely by a disturbed immune system.…”

Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

“…An important role for mitochondrial dysfunction in the pathogenesis of systemic lupus erythematous (SLE) has been described by our group and by others (for review, see ref. 1). Enhanced synthesis of mitochondrial reactive oxygen species (mROS) by lupus neutrophil subsets is associated with enhanced formation of neutrophil extracellular traps (NETs) that are enriched in oxidized mitochondrial DNA (mDNA).…”

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

“…Complex etiological factors are involved in lupus pathogenesis, such as genetic predisposition [28,29,30,31], epigenetic post-transcriptional regulation [32,33,34,35,36], sex hormone imbalance [37,38], environmental stimulation [39,40], mental/psychological stresses [38], and other undefined factors [41]. Recently, many authors have demonstrated that mitochondrial dysfunctions [42,43,44,45,46], defective bioenergetics in immune cells, and abnormal immunometabolism [47,48] can induce structural and functional changes of biomolecules (proteins, lipids, nucleic acids, and glycoproteins) by oxidative and nitrosative stresses [49,50]. All of these precipitating factors can potentially accelerate immunosenescence by way of inflammaging in patients with SLE [8,51,52].…”