Selective autophagy of intracellular organelles: Recent research advances

Abstract

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, etc . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, etc . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.

Simvastatin accelerated motoneurons death in SOD1G93A mice through inhibiting Rab7-mediated maturation of late autophagic vacuoles

“…Autophagy can be envisaged as a process to consist of autophagosomal formation, targeted transport, and fusion with lysosome that degraded cytosolic components engulfed in autophagic membranes 7 , 8 . AP formation is facilitated by p62 interacting LC3 to encase pathogens in APs 3 .…”

“…Macroautophagy (hereafter autophagy) is an important lysosomal degradation route in which cytosolic components, especially long-lived or misfolded/aggregate-prone proteins, damaged whole organelles, are effectively removed and recycled 7 . Autophagy involves the sequestration of cytoplasmic materials into a double-membrane autophagosomes (APs) and subsequent delivery to lysosomes for catabolism 8 .…”

Neuroinflammation in Alzheimer’s Disease

“…Cells degrade protein aggregates and damaged organelles by autophagy and defective mitochondria by mitophagy [ 185 , 186 , 187 , 188 ]. With advancing age, autophagy gradually subsides and this decline is linked to defective mitochondria and results in inflammaging [ 189 ].…”

Autophagy: A Friend or Foe in Allergic Asthma?

“…Selective autophagy also monitors lipid imbalance, glucose scarcity, amino acid deprivation, and iron shortage and facilitates metabolic reprogramming. Other types of selective autophagy include the capacity to clear intracellular pathogens (xenophagy), the degradation of damaged mitochondria (mitophagy), endoplasmic reticulum (ER-phagy), peroxisomes (pexophagy), polyubiquitinated aggregates (aggrephagy), ribosomes (ribophagy), lipid droplets (lipophagy), and cilia components (ciliophagy) [3].…”