Dissecting the role of alternative splicing in the regulation of autophagy: a narrative review

Alternative splicing plays a pivotal role in the posttranscriptional regulation of gene expression, contributing to the generation of proteome diversity. Autophagy is a conserved cellular machinery governing degradation and recycling of long-lived or damaged proteins and organelles. However, there is limited knowledge of the roles of alternative splicing in autophagy, in particular mitochondrial selective autophagy, termed mitophagy. Emerging evidence suggests autophagy-related proteins (Atg), key molecules in autophagy process, are involved. This review highlights recent advances in the understanding of mechanisms by which alternative splicing affects the functions of ATG genes including BECN1, ATG5, ATG16L1, and Bim genes, and thus manipulates autophagy levels in various diseases. This review found that the effects of splicing of ATG genes generally result in inhibiting autophagy. However, very few of the many autophagy associated proteins have been studied. More research into the transcriptional and post-transcriptional regulation of splicing factors will be necessary to understand their roles in pathological conditions associated with autophagy and mitophagy.