Life sciences · 2025
The role of TP53INP2 as an adaptor protein in the regulation of lipophagy in mature adipocytes.
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Sekar Mouliganesh, Thirumurugan Kavitha
Аннотация
AIM: Lipid droplet (LD) accumulation is caused by an imbalance between energy intake and expenditure, leading to adipose tissue dysfunction, obesity, and other metabolic disorders. Lipophagy is a selective autophagy process responsible for LD degradation. However, no specific adaptor proteins have been identified as regulators of lipophagy. This study investigates the role of TP53INP2 as a potential adaptor protein in the regulation of the lipophagy process.
METHODS: Murine 3T3L1 cells were subjected to starvation treatment to stimulate autophagy, followed by gene and protein expression analysis to evaluate markers associated with autophagy, adipogenesis, and lipophagy, providing insights into lipid degradation and the lipophagy process. Co-IP analysis of autophagy receptors and lipophagy adaptor proteins provided evidence supporting TP53INP2's role as a potential adaptor protein. Additionally, siRNA-mediated TP53INP2 knockdown further validated its function in lipophagy regulation.
KEY FINDINGS: Our findings demonstrated that TP53INP2 negatively regulates adipocyte differentiation while promoting autophagy. In mature adipocytes, TP53INP2 actively promotes lipophagy by targeting LDs through interaction with the membranous protein perilipin 1 (PLIN1). The Co-IP analysis confirmed that TP53INP2 directly binds to PLIN1 and the autophagosome receptor LC3 via its LIR motif. Furthermore, TP53INP2 knockdown in mature adipocytes impaired lipophagy, preventing the degradation of PLIN1 despite the continued function of general autophagy through the common adaptor protein p62 with LC3. These findings suggest that TP53INP2 may serve as an adaptor protein in regulating lipophagy in mature adipocytes.
METHODS: Murine 3T3L1 cells were subjected to starvation treatment to stimulate autophagy, followed by gene and protein expression analysis to evaluate markers associated with autophagy, adipogenesis, and lipophagy, providing insights into lipid degradation and the lipophagy process. Co-IP analysis of autophagy receptors and lipophagy adaptor proteins provided evidence supporting TP53INP2's role as a potential adaptor protein. Additionally, siRNA-mediated TP53INP2 knockdown further validated its function in lipophagy regulation.
KEY FINDINGS: Our findings demonstrated that TP53INP2 negatively regulates adipocyte differentiation while promoting autophagy. In mature adipocytes, TP53INP2 actively promotes lipophagy by targeting LDs through interaction with the membranous protein perilipin 1 (PLIN1). The Co-IP analysis confirmed that TP53INP2 directly binds to PLIN1 and the autophagosome receptor LC3 via its LIR motif. Furthermore, TP53INP2 knockdown in mature adipocytes impaired lipophagy, preventing the degradation of PLIN1 despite the continued function of general autophagy through the common adaptor protein p62 with LC3. These findings suggest that TP53INP2 may serve as an adaptor protein in regulating lipophagy in mature adipocytes.