Autophagy and mitochondrial function regulators

Autophagy and mitochondrial function regulators comprise a diverse group of proteins, including kinases like AMPK and mTOR, that coordinate cellular energy status with organelle quality control [Hardie et al., Nature Reviews Molecular Cell Biology, 2012]. These regulators facilitate mitophagy, the selective degradation of damaged mitochondria, which is essential for preventing oxidative stress and maintaining metabolic efficiency [Palikaras et al., Nature Cell Biology, 2018]. In neurodegenerative conditions such as Parkinson's disease, mutations in regulators like PINK1 or Parkin lead to the accumulation of dysfunctional mitochondria and subsequent neuronal loss [Pickrell & Youle, Neuron, 2015]. Therapeutic strategies targeting these pathways include mTOR inhibitors (e.g., Rapamycin) to induce autophagy and AMPK activators (e.g., Metformin) to promote mitochondrial biogenesis [Galluzzi et al., Nature Reviews Drug Discovery, 2017]. While promising for treating aging and metabolic diseases, the broad physiological roles of these regulators present challenges regarding systemic toxicity and the potential for unintended effects on cell survival in cancer contexts [Klionsky et al., Autophagy, 2021].

Other names

Mitophagy regulatorsMitochondrial quality control (MQC) factorsAutophagy-lysosome pathway (ALP) modulatorsMitochondrial homeostasis regulatorsAutophagy-mitochondria axis regulators

Pharmacological agents modulate these regulators by inhibiting the mTORC1 complex to release the brake on autophagy, activating AMPK to stimulate mitochondrial biogenesis and ULK1-mediated autophagy, or inducing the PINK1/Parkin pathway to facilitate the clearance of damaged mitochondria [Hardie et al., 2012; Galluzzi et al., 2017].