Autophagy regulatory molecule, TMEM74, interacts with BIK and inhibits BIK-induced apoptosis.

TMEM74 (Transmembrane protein 74), a lysosome transmembrane protein, induces cell autophagy. Knockdown of TMEM74 abolished EBSS-induced autophagy. BIK, belonging to BOP (BH3-only protein) protein family, has been reported to induce cell apoptosis. Autophagy and apoptosis, as different pathways regulated by extra- or intra-cellular signals precisely, both play a crucial role in processes of intra-cellular substrates degradation, energy metabolism and cell survival. However, the relationship between autophagy and apoptosis still remains elusive. To elucidate the putative new relationship and further identify the function of TMEM74, we performed the study mainly using co-immunoprecipitation, immunoblotting, fluorescent location and basic cell biologic experimental techniques. In the present study, for the first time, it is demonstrated that autophagy-related protein TMEM74 co-localizes with apoptosis-related protein BIK in subcellular organelles. The data indicated that TMEM74 associates with BIK via TM domains of TMEM74 and BH3 domain of BIK. Further investigations revealed that TMEM74 inhibits BIK-induced apoptosis by interacting with BIK, as evidenced by the results that autophagosome formation inhibitor could not block the inhibition effect completely. On the contrary, knockdown of TMEM74 and the TM domain-deficient mutant led to deprivation of the function. Overall, the results revealed the autophagy modulator TMEM74 interrelates with apoptosis inducer BIK and inhibits its function, which provides a novel crosstalk point between autophagy and apoptosis to enlarge our understanding of the programmed cell death.