Autophagy and mitophagy regulatory pathway (null)

Autophagy and mitophagy regulatory pathways comprise an extensive network of signaling molecules and protein complexes that orchestrate the degradation of cytoplasmic contents (autophagy) and the selective removal of damaged mitochondria (mitophagy)[1][4][5][6]. Autophagy is regulated by stress signals, nutrient status, and energy sensing—centrally by kinases such as mTOR (negative regulator) and AMPK (positive regulator)[3][4][5]. Canonical initiation involves the ULK1 complex (in mammals), which integrates upstream signals to assemble the core autophagy machinery. Mitophagy specificity is achieved through additional proteins, including PINK1 and Parkin (ubiquitin-dependent pathway), NIX, BNIP3, FUNDC1, and others (receptor-mediated pathways), which target mitochondria for degradation by linking to autophagosome adapter proteins like LC3[1][5][4]. Dysregulation of these pathways is implicated in aging, cancer, neurodegeneration, and cardiovascular diseases. Because these pathways incorporate multiple protein targets with different molecular classifications, their modulation represents a promising therapeutic strategy as well as a challenge for specific drug intervention[1][5][6][3].

Other names

Autophagy pathwayMitophagy pathwayMacroautophagy pathwayMitochondrial autophagy pathway

mTOR inhibition increases autophagy AMPK activation promotes autophagy Direct activation/inhibition of autophagy/mitophagy specific proteins (e.g., Parkin, PINK1, Beclin-1, ULK1 complex) Blocking mitochondrial fission reduces mitophagy