Mitochondrion-associated protein LRPPRC suppresses the initiation of basal levels of autophagy via enhancing Bcl-2 stability

The mitochondrion-associated protein LRPPRC interacts with one of microtubule-associated protein family MAP1S (originally named as C19ORF5) to form a complex. MAP1S interacts with LC3, the mammalian homologue of yeast autophagy marker ATG8 and one of the most important autophagy markers in mammalian cells, and helps the attachment of autophagosomes with microtubules for trafficking and recruitment of substrate mitochondria into autophagosomes for degradation. MAP1S activates autophagosomal biogenesis and degradation to remove mis-folded/aggregated proteins and dysfunctional organelles such as mitochondria and suppress oxidative stress-induced genomic instability and tumorigenesis. Previously, various studies have attributed LRPPRC nuclear acid-associated functions. Instead, here we show that LRPPRC associates with mitochondria, interacts with Beclin 1 and Bcl-2 and forms a ternary complex to maintain the stability of Bcl-2. Suppression of LRPPRC leads to reduction of mitochondrial potential and reduction of Bcl-2. Lower levels of Bcl-2 lead to release of more Beclin 1 to form the Beclin 1-PI3KCIII complex to activate autophagy and accelerate the turnover of dysfunctional mitochondria through the PI3K-AKT-mTOR pathway. The activation of autophagy induced by LRPPRC suppression occurs upstream of the ATG5-ATG12 conjugates-mediated conversion of LC3-I to LC3-II and has been confirmed in multiple mammalian cell lines with multiple autophagy markers including size of GFP-LC3 puncat...
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research