scholarly journals The Mitochondrial Fission Regulator DRP1 Controls Post-Transcriptional Regulation of TNF-α

2021 ◽  
Vol 10 ◽  
Author(s):  
Fushan Gao ◽  
Mack B. Reynolds ◽  
Karla D. Passalacqua ◽  
Jonathan Z. Sexton ◽  
Basel H. Abuaita ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Critical Role ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Proinflammatory Response ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Tnf Α

The mitochondrial network plays a critical role in the regulation of innate immune signaling and subsequent production of proinflammatory cytokines such as IFN-β and IL-1β. Dynamin-related protein 1 (DRP1) promotes mitochondrial fission and quality control to maintain cellular homeostasis during infection. However, mechanisms by which DRP1 and mitochondrial dynamics control innate immune signaling and the proinflammatory response are incompletely understood. Here we show that macrophage DRP1 is a positive regulator of TNF-α production during sterile inflammation or bacterial infection. Silencing macrophage DRP1 decreased mitochondrial fragmentation and TNF-α production upon stimulation with lipopolysaccharide (LPS) or methicillin-resistant Staphylococcus aureus (MRSA) infection. The defect in TNF-α induction could not be attributed to changes in gene expression. Instead, DRP1 was required for post-transcriptional control of TNF-α. In contrast, silencing DRP1 enhanced IL-6 and IL-1β production, indicating a distinct mechanism for DRP1-dependent TNF-α regulation. Our results highlight DRP1 as a key player in the macrophage pro-inflammatory response and point to its involvement in post-transcriptional control of TNF-α production.

scholarly journals Mitochondrial Modulations, Autophagy Pathways Shifts in Viral Infections: Consequences of COVID-19

2021 ◽  
Vol 22 (15) ◽  
pp. 8180
Author(s):  
Shailendra Pratap Singh ◽  
Salomon Amar ◽  
Pinky Gehlot ◽  
Sanjib K. Patra ◽  
Navjot Kanwar ◽  
...  
Keyword(s):  
Cell Death ◽  
Essential Role ◽  
Viral Infections ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Innate Immune ◽  
Innate Immune Signaling ◽  
Promising Target ◽  
Intracellular Organelles ◽  
Viral Proliferation

Mitochondria are vital intracellular organelles that play an important role in regulating various intracellular events such as metabolism, bioenergetics, cell death (apoptosis), and innate immune signaling. Mitochondrial fission, fusion, and membrane potential play a central role in maintaining mitochondrial dynamics and the overall shape of mitochondria. Viruses change the dynamics of the mitochondria by altering the mitochondrial processes/functions, such as autophagy, mitophagy, and enzymes involved in metabolism. In addition, viruses decrease the supply of energy to the mitochondria in the form of ATP, causing viruses to create cellular stress by generating ROS in mitochondria to instigate viral proliferation, a process which causes both intra- and extra-mitochondrial damage. SARS-COV2 propagates through altering or changing various pathways, such as autophagy, UPR stress, MPTP and NLRP3 inflammasome. Thus, these pathways act as potential targets for viruses to facilitate their proliferation. Autophagy plays an essential role in SARS-COV2-mediated COVID-19 and modulates autophagy by using various drugs that act on potential targets of the virus to inhibit and treat viral infection. Modulated autophagy inhibits coronavirus replication; thus, it becomes a promising target for anti-coronaviral therapy. This review gives immense knowledge about the infections, mitochondrial modulations, and therapeutic targets of viruses.

scholarly journals Innate Immune Signaling in Regulation of Immunity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-26-SCI-26
Author(s):  
Giorgio Trinchieri
Keyword(s):  
Tumor Progression ◽  
Adaptive Immunity ◽  
Cancer Biology ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Innate Immune ◽  
Immune Signaling ◽  
Innate Resistance ◽  
Innate Immune Signaling

Abstract Innate resistance, as an integral part of inflammation, and adaptive immunity participate in oncogenesis and tumor surveillance. For a long time, innate resistance was considered a primitive nonspecific form of resistance to infections that was eclipsed by the potent and specific acquired immunity of higher organisms. More recently, it has been recognized that innate resistance is not only the first line of defense against infections but also sets the stage and is necessary for the development of adaptive immunity. Advances in cancer biology have revealed that the defensive mechanisms of innate resistance and inflammation are indeed manifestations of tissue homeostasis and control of cellular proliferation that have many pleiotropic effects on carcinogenesis and tumor progression and dissemination. The interaction of innate and adaptive immunity with carcinogenesis and tumor progression is complicated and results in effects that either favor or impede tumor progression. Innate immune receptors both sense and regulate the composition of the microbiota, the large number of commensal microorganisms that colonize the barrier surfaces of all multicellular organisms, including those of humans. The microbiota affects many functions of our body and the two together comprise one metaorganism. Microbial imbalance particularly in the gut plays a critical role in the development of multiple diseases, such as cancer, autoimmune conditions and increased susceptibility to infection. Alteration in innate immune signaling and immunity may change the composition of the microbiota affecting tumor initiation both at the barrier sites (e.g. in the gut) and systemically. The commensal microbes not only may affect the development and progression of cancer but they have also important effects on the response to cancer therapy. Mostly through their interaction with innate receptors, commensal microorganisms modulate the ability of the organism to respond to cancer immunotherapy and chemotherapy by affecting the threshold of response of tumor-associated myeloid cells and their ability to sustain anti-tumor immunity. Disclosures No relevant conflicts of interest to declare.

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