Fig. 1: The role of mitochondria in innate immune activation of DNA- and RNA-sensing pathways. | npj Metabolic Health and Disease

Fig. 1: The role of mitochondria in innate immune activation of DNA- and RNA-sensing pathways.

From: Mitochondrial dysfunction in acute and post-acute phases of COVID-19 and risk of non-communicable diseases

Fig. 1

Cytosolic RNA can activate retinoic acid-inducible gene I (RIG-I), enabling Mitochondrial antiviral signaling protein (MAVS) to bind and oligomerize, thereby allowing TANK-binding kinase 1 (TBK1) to bind and phosphorylate MAVS. Downstream Interferon regulatory factor 3 (IRF3) is activated and translocates to the nucleus to induce the transcription of type 1 IFN genes. Likewise, cytosolic DNA can activate stimulator of interferon response cGAMP interactor 1 (STING) via the second messenger 2'3’-cyclic GMP-AMP (cGAMP) produced by cyclic GMP–AMP synthase (cGAS). STING then translocates from the endoplasmatic reticulum to the golgi to bind TBK1, and subsequently activates IRF3. Alternatively, both pathways can lead to activation of Nuclear Factor Kappa B (NF-Ƙb) to orchestrate a more pro-inflammatory response. Mitochondria play a dual role in these pathways, as they host the MAVS protein, which activation is directly dependent on mitochondrial health, and mitochondrial DNA (mtDNA) can be released from compromised mitochondria to activate DNA-sensing pattern recognition receptors such as cGAS.

Back to article page