Autophagy
Specificities
Selective Autophagy: Targets specific cellular components such as damaged mitochondria (mitophagy), peroxisomes (peroxiphagy), or bacteria (xenophagy).
Non-selective Autophagy: Bulk degradation process, often induced by nutrient starvation or stress.
Selective Autophagy: Targets specific cellular components such as damaged mitochondria (mitophagy), peroxisomes (peroxiphagy), or bacteria (xenophagy).
Non-selective Autophagy: Bulk degradation process, often induced by nutrient starvation or stress.
Indicators
LC3-II Conversion: Common marker indicating the formation of autophagosomes.
p62/SQSTM1 Degradation: Reflects autophagic flux by monitoring protein degradation.
LC3-II Conversion: Common marker indicating the formation of autophagosomes.
p62/SQSTM1 Degradation: Reflects autophagic flux by monitoring protein degradation.
Inhibitors and Inducers
Inducers: Rapamycin, nutrient starvation, and metformin.
Inhibitors: Chloroquine, 3-Methyladenine, and Bafilomycin A1.
Inducers: Rapamycin, nutrient starvation, and metformin.
Inhibitors: Chloroquine, 3-Methyladenine, and Bafilomycin A1.
Related Genes and Proteins
ATG Genes (Autophagy-related genes): Essential for autophagosome formation and maturation.
Beclin-1: Key regulatory protein involved in initiation of autophagy.
ATG Genes (Autophagy-related genes): Essential for autophagosome formation and maturation.
Beclin-1: Key regulatory protein involved in initiation of autophagy.
Mechanisms of Change of Autophagic Activity
mTOR Pathway: Central regulator that is nutrient-sensitive, negatively regulates autophagy.
AMPK Pathway: Activated by cellular energy depletion, promotes autophagy by inhibiting mTOR.
mTOR Pathway: Central regulator that is nutrient-sensitive, negatively regulates autophagy.
AMPK Pathway: Activated by cellular energy depletion, promotes autophagy by inhibiting mTOR.
Organella Relations to Autophagy
Mitochondria (Mitophagy): Removal of damaged mitochondria, crucial for cellular health and metabolic efficiency.
Endoplasmic Reticulum (ER-phagy): Degradation of portions of the endoplasmic reticulum under stress.
Lysosomes: Central organelles that fuse with autophagosomes to degrade their content.
Mitochondria (Mitophagy): Removal of damaged mitochondria, crucial for cellular health and metabolic efficiency.
Endoplasmic Reticulum (ER-phagy): Degradation of portions of the endoplasmic reticulum under stress.
Lysosomes: Central organelles that fuse with autophagosomes to degrade their content.
Therapeutic Approaches
Cancer: In the context of cancer, autophagy plays a dual role; it can suppress tumor initiation by eliminating damaged organelles and proteins, but can also promote tumor survival and growth under metabolic stress by providing nutrients through the recycling of cellular components.
Neurodegenerative Diseases: Enhancing autophagy has been shown to alleviate symptoms and pathology in models of diseases such as Alzheimer's, Parkinson's, and Huntington's diseases, suggesting a protective role against neurodegeneration.
Aging: By reducing the accumulation of toxic aggregates and dysfunctional components, autophagy helps to prevent cellular stress and inflammation, key contributors to aging.
Cancer: In the context of cancer, autophagy plays a dual role; it can suppress tumor initiation by eliminating damaged organelles and proteins, but can also promote tumor survival and growth under metabolic stress by providing nutrients through the recycling of cellular components.
Neurodegenerative Diseases: Enhancing autophagy has been shown to alleviate symptoms and pathology in models of diseases such as Alzheimer's, Parkinson's, and Huntington's diseases, suggesting a protective role against neurodegeneration.
Aging: By reducing the accumulation of toxic aggregates and dysfunctional components, autophagy helps to prevent cellular stress and inflammation, key contributors to aging.
