The autophagy, which can be regulated by lysosomal membrane proteins, plays a critical role in maintaining normal podocyte function. TM7SF1 is a novel lysosomal membrane protein, but its effect on autophagy is still unknown. This study aimed to identify the role of TM7SF1 in mouse podocyte (MPC5) autophagy. Interestingly, we detected an increase in LC3BII and SQSTM1/P62 in MPC5 through inhibiting TM7SF1, and which can be completely corrected after blocking the autolysosome degradation with chloroquine (CQ). Moreover, inhibition of TM7SF1 expression did not increase the mRNA level of SQSTM1/P62. Theses results suggested that inhibition of TM7SF1 led to impaired degradation of autophagy products, which manifest as an abnormal accumulation of LC3BII and SQSTM1/P62. Further studies showed that the downregulation of TM7SF1 resulted in a significant decrease in the number of acid lysosomes, which directly led to decreases in the number and function of autolysosomes. In conclusion, TM7SF1 is therefore essential for autolysosomes degradation pathway at the end of autophagy flow, and for the maintenance of podocyte function.

可以通过溶酶体膜蛋白调节的自噬在维持正常足细胞功能中起着至关重要的作用。TM7SF1是一种新型的溶酶体膜蛋白，但其对自噬的影响尚不清楚。这项研究旨在确定TM7SF1在小鼠足细胞（MPC5）自噬中的作用。有趣的是，我们通过抑制TM7SF1检测到MPC5中LC3BII和SQSTM1 / P62的增加，在用氯喹（CQ）阻止自溶酶体降解后可以完全纠正。此外，TM7SF1表达的抑制并不增加SQSTM1 / P62的mRNA水平。这些结果表明抑制TM7SF1导致自噬产物的降解受损，这表现为LC3BII和SQSTM1 / P62的异常积累。进一步的研究表明，TM7SF1的下调导致酸性溶酶体的数量显着减少，这直接导致自溶酶体的数量和功能下降。总之，因此，TM7SF1对于自噬流结束时的溶酶体降解途径以及维持足细胞功能至关重要。