# Autophagy Regulates Putative Anion Transporter 1 Expression in Intestinal Epithelial Cells

## TL;DR

This study shows that autophagy, a cellular cleanup process, regulates the levels of a key transporter involved in oxalate balance in intestinal cells.

## Contribution

The paper reveals a novel role of autophagy in controlling PAT-1 protein levels in intestinal epithelial cells.

## Key findings

- Rapamycin and nutrient deprivation reduced PAT-1 protein levels in Caco-2 cells.
- ATG7 knockdown increased PAT-1 levels in both cells and ATG7KO mice.
- Autophagy induction was confirmed by increased LC3II/I ratio and decreased p62 levels.

## Abstract

Putative anion transporter 1 (PAT‐1) is the key oxalate‐secreting transporter in the intestine and therefore, maintaining its steady‐state levels is critical for oxalate homeostasis. Autophagy is known to modulate the expression of intestinal solute transporters; however, its role in regulating PAT‐1 has not been examined. Autophagy in Caco‐2 cells was induced by either rapamycin treatment or by nutrient deprivation and assessed by conventional autophagy marker proteins. ATG7 (autophagy‐related 7) protein expression was attenuated by ATG7‐siRNA in Caco‐2 cells or by utilising ATG7KO mice. PAT‐1 protein levels in Caco‐2 cells were significantly reduced by rapamycin or by nutrient deprivation at 48 and 72 h. Concomitantly, the LC3II/I ratio was increased, and p62 levels were significantly decreased, confirming the induction of autophagy. Nutrient deprivation for 6 h also caused a significant decrease in the surface levels of PAT‐1. PAT‐1 protein levels were increased by the siRNA‐mediated ATG7 knockdown in Caco‐2 cells and in the ileum of ATG7KO mice. In summary, Autophagy in intestinal epithelial cells modulates the basal levels of PAT‐1 protein and may play a critical role in the maintenance of oxalate homeostasis.