Reticulon-dependent ER-phagy mediates adaptation to heat stress in C. elegans

Area of Science:

• Cellular Biology
• Autophagy Research
• Stress Response Mechanisms

Background:

• Endoplasmic reticulum (ER) homeostasis is crucial for cell function.
• Autophagy, a cellular degradation process, plays a role in maintaining ER homeostasis through ER-phagy.
• Different types of ER-phagy utilize specific autophagy receptors depending on the ER stressor.

Purpose of the Study:

• To identify novel mechanisms and receptors involved in ER-phagy.
• To investigate the role of ER-phagy in adaptation to acute heat stress.
• To elucidate the function of the reticulon long isoform (RET-1d) in ER-phagy.

Main Methods:

• Induction of macroER-phagy via heat stress in C. elegans.
• Identification and characterization of the RET-1d protein as an ER-phagy receptor.
• Analysis of RET-1d's interaction with LGG-1/GABARAP using LC3-interacting region (LIR) motifs.
• Depletion and mutation studies of RET-1d and LIRs to assess ER-phagy function.
• Evaluation of animal adaptation capacity to heat stress.

Main Results:

• A novel macroER-phagy pathway induced by tubular ER fragmentation during heat stress was identified.
• The reticulon long isoform (RET-1d) was identified as a key ER-phagy receptor, primarily expressed in nervous system and epidermis.
• RET-1d interacts with the autophagy protein LGG-1/GABARAP via two LIR motifs.
• Depletion of RET-1d or mutation of its LIRs impaired ER-phagy and reduced heat stress adaptation.
• A RET-1d- and LGG-1-dependent ER-phagy mechanism in neurons and epidermis was revealed.

Conclusions:

• RET-1d acts as a crucial receptor mediating ER-phagy in response to heat stress.
• This RET-1d/LGG-1 dependent ER-phagy pathway is vital for neuronal and epidermal function under stress.
• The identified ER-phagy mechanism contributes significantly to the adaptation of C. elegans to acute heat stress.