The role of mitophagy in innate immune responses triggered by mitochondrial stress

Abstract

Mitochondria are important cellular organelles involved in many different functions, from energy generation and fatty acid oxidation to cell death regulation and immune responses. Accumulating evidence indicates that mitochondrial stress acts as a key trigger of innate immune responses. Critically, the dysfunctional mitochondria can be selectively eliminated by mitophagy. The elimination of dysfunctional mitochondria may function as an effective way employed by mitophagy to keep the immune system in check. In addition, mitophagy can be utilized by pathogens for immune evasion. In this review, we summarize how mitochondrial stress triggers innate immune responses and the roles of mitophagy in innate immunity and in infection, as well as the molecular mechanisms of mitophagy. Graphical abstract

Insights into early stages of the establishment of host:algal endosymbioses: Genetic responses to live versus heat-killed algae and bacterial prey in a sponge host

“…5 and 9). This gene plays roles in protecting cells from stress-induced mitochondrial dysfunction by setting the stage for mitophagy as part of the innate immune response (Song, Zhou & Zhou, 2020). PINK1 has a wide variety of functions in human systems including regulation of cell metabolism, cancer development and inflammation as well as being responsible for the pathogenesis of early-onset Parkinson’s disease.…”

NIPSNAP protein family emerges as a sensor of mitochondrial health

“…In vitro/ HEK293 cells [13] Bone morphogenetic proteins (BMP) Xenopus [21,22] BMP Associated with lens generation Xenopus [22] Trichostatin A In vitro/ hepatoma cell lines [23] Umbelliprenin Anti-tumor activity In vitro/ QU-DB cells [24] Finasteride and dutasteride Neuroprotective role [25] Mitochondrial DNA (mtDNA) mtDNA maintenance In vitro…”

“…[97] Immune response: Mitochondrial damage can trigger innate immune response resulting in production of proinflammatory cytokines and type I interferon. [21] Mitophagy has been shown to inhibit endotoxin induced production of pro-inflammatory cytokines. [22] Also, PINK1-PARKIN mediated mitophagy inhibits innate immunity and type I interferon responses.…”

Mitochondrial Nucleic Acid as a Driver of Pathogenic Type I Interferon Induction in Mendelian Disease

“…Remarkably, an increasing number of situations associated with mitochondrial stress have been linked to the release and sensing of mtNA, mostly mtDNA through cGAS-STING, and the induction of IFN ( 28 ). These include environmental insults, oxidative stress, ‘suboptimal’ mitochondrial function, mitochondrial dysfunction due to mutations (mitochondrial disease detailed below), proteotoxic stress, and infection ( 24 , 25 , 30 ). Such stress, typically evidenced by impaired oxidative phosphorylation and ATP production, metabolic imbalance, loss of mitochondrial potential and mROS induction, results in a loss of mitochondrial integrity and release of mitochondrial components.…”

“…For example, these molecules can engage the inflammasome, resulting in interleukin 1β (IL1β)-mediated inflammation ( 22 – 25 ) and endosomal Toll-like receptor 9 (TLR9) activation, leading to IFN and NF-κB-dependent inflammatory cytokine induction ( 26 , 27 ). These pathways, also implicated in inflammatory diseases, are specific to discrete cell types and have been extensively reviewed elsewhere ( 15 , 24 , 25 , 28 , 29 ). mtDNA can also be released into the extracellular space, acting as a plasmatic marker and driver of systemic inflammation in autoimmunity, traumatic injury, lung inflammation and cardiovascular disease ( 30 , 31 ).…”