Fig. 2

Mitochondria as a multifaceted hub of the brain pathophysiology. a Under cellular stresses, mitochondrial outer membrane permeabilization leads to release of cyto c and ROS, activating the downstream pathways of apoptosis and necroptosis. Ferroptosis is also induced by mitochondrial ETC-promotive lipid peroxide. Pyroptosis is the downstream signal of mitochondrial dysfunctions, and is controlled by mitochondria to initiate apoptosis/necrosis. b Mitochondria contain endogenous inflammatory inducers, including mtDNA, mtRNA, metabolic products and ROS. Mitochondria outer membrane acts as a platform for immune signaling through inflammasome and MAVS activation. MAVS also endows cells with antiviral immunity. c Mitochondria participate in multiple steps of autophagy including autophagy initiation, phagophore elongation, autophagic flux formation and autophagy gene induction. d Mitochondria participate in cellular communication in the brain through membrane contact and cellular organelle transfer. α-syn, α-synuclein; Aβ, β-amyloid; ATP, adenosine triphosphate; cyto c, cytochrome c; ETC, electron transport chain; GSH, glutathione; MAVS, mitochondrial antiviral signaling; ROS, reactive oxygen species; TDP-43: TAR DNA-binding protein 43; TGF-β, transforming growth factor β; VEGF, vascular endothelial growth factor