1.
The role of mitophagy in pulmonary sepsis.
Mohsin, M, Tabassum, G, Ahmad, S, Ali, S, Ali Syed, M
Mitochondrion. 2021;:63-75
Abstract
Sepsis is a systemic inflammatory disease with an unacceptably high mortality rate caused by an infection or trauma that involves both innate and adaptive immune systems. Inflammatory events activate different downstream pathways leading to tissue damage and ultimately multi-organ failure. Mitochondria are responsible for cellular energy, thermoregulation, metabolite biosynthesis, intracellular calcium regulation, and cell death. Damaged mitochondria induce the high Ca2+ influx through mitochondrial calcium uniporter (MCU). It also generates excessive Reactive oxygen species (ROS) and releases mtDNA into the cytoplasm, which causes induction of NLRP3 inflammasome and apoptosis. Mitophagy (Autophagy of damaged mitochondria) controls mitochondrial dynamics and function. It also maintains cellular homeostasis. This review is about how pulmonary sepsis affects the body. What is the aftermath of sepsis, and how mitophagy affects Acute Lung Injury and macrophage polarisation to overcome the damages.
2.
Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment.
Mehta, SR, Pérez-Santiago, J, Hulgan, T, Day, TR, Barnholtz-Sloan, J, Gittleman, H, Letendre, S, Ellis, R, Heaton, R, Patton, S, et al
Journal of neuroinflammation. 2017;(1):72
Abstract
BACKGROUND Mitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. METHODS We quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS < 0.5, unimpaired). CSF, clinical, and biomarker data from the earliest available time point were analyzed. Cell-free mtDNA associations with CSF inflammation and iron-related biomarkers [CXCL10, IL-6, IL-8, TNF-a, transferrin (TF), ceruloplasmin (CP), and vascular endothelial growth factor (VEGF)], VL, and GDS were evaluated by multivariable regression. RESULTS CSF cell-free mtDNA levels were significantly lower in participants with undetectable (vs. detectable) VL in either plasma (p < 0.001) or CSF (p < 0.001) and in those on antiretroviral therapy (ART; p < 0.001). Participants on ART with undetectable VL in both CSF and plasma had lower mtDNA levels than those with detectable VL in both compartments (p = 0.001). Higher mtDNA levels were observed in participants in the highest vs. lowest tertile (T3 vs. T1) of CSF CXCL10 (T3 vs. T1, p < 0.001) and TNF-a (T3 vs. T1, p < 0.05) in unadjusted analyses. MtDNA levels also correlated with CSF leukocyte count. After adjusting for CSF leukocyte count and VL, mtDNA levels were also associated with other inflammation- and iron-related biomarkers in CSF, including TF (T3 vs. T1, p < 0.05) and CP (T3 vs. T1, p < 0.05). With additional correction for ART use, mtDNA was also negatively associated with CSF VEGF (p < 0.05) and IL-6 (p = 0.05). We observed no associations of CSF mtDNA levels with age or GDS-defined NC impairment. CONCLUSIONS CSF cell-free mtDNA levels were associated with HIV RNA and ART status, as well as with biomarkers of iron transport and VEGF, a growth factor with known effects on mitochondrial integrity and autophagy. CSF mtDNA may be a biomarker of iron dysregulation and/or neuroinflammation during HIV infection.
3.
Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.
Nasi, M, Cristani, A, Pinti, M, Lamberti, I, Gibellini, L, De Biasi, S, Guazzaloca, A, Trenti, T, Cossarizza, A
International journal of sports physiology and performance. 2016;(1):116-21
Abstract
PURPOSE Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. METHODS Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. RESULTS The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. CONCLUSIONS Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.