Biology subjects

Kuma, A.

Publications and source records attributed to Kuma, A..

3 recordsLinked to original sources

bioRxiv2024

The Rubicon-WIPI axis regulates exosome biogenesis during aging

Cells release intraluminal vesicles (ILVs) in multivesicular bodies as exosomes to communicate with other cells. Although recent studies suggest an intimate link between exosome biogenesis and autophagy, the detailed mechanism is not fully understood. Here we employed comprehensive RNAi screening for autophagy-related factors and discovered that Rubicon, a negative regulator of autophagy, is essential for exosome release. Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Interactome analysis of WIPI2d identified the ESCRT components that are required for ILV formation. Notably, we found that Rubicon is required for an age-dependent increase of exosome release in mice. In addition, small RNA sequencing of serum exosomes revealed that Rubicon determines the fate of exosomal microRNAs associated with cellular senescence and longevity pathways. Taken together, our current results suggest that the Rubicon-WIPI axis functions as a key regulator of exosome biogenesis and is responsible for the age-dependent changes in exosome quantity and quality.

cell biology↗

bioRxiv2023

Golgi membrane proteins YIPF3 and YIPF4 regulate turnover of the Golgi apparatus through autophagy

The degradation of organelles by autophagy is essential for cellular homeostasis. The Golgi apparatus has recently been demonstrated to be degraded by autophagy, but little is known about how the Golgi is recognized by the autophagosome. Using quantitative proteomic analysis and two Golgiphagy-reporter systems that we developed, we found that five-transmembrane Golgi-resident proteins, YIPF3 and YIPF4, constitute a Golgiphagy receptor. The YIPF3-YIPF4 complex interacts with LC3B, GABARAP, and GABARAPL1 via the LIR motif in YIPF3, whose stability is dependent on YIPF4. Phosphorylation of the LIR in YIPF3 seems to be required for YIPF3-ATG8 interaction. Moreover, expression of the YIPF3 LIR mutant caused an elongated Golgi morphology, indicating the importance of Golgi turnover via selective autophagy. The reporter assays that we established will pave the way for future studies to obtain deeper insights into Golgiphagy.

cell biology↗

bioRxiv2019

Autophagy controls lipid droplet formation by fine-tuning NCoR1 levels

Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, such as following a meal. LDs serve as an energy reservoir during fasting and have a buffering capacity that prevents lipotoxicity. Autophagy and the autophagic machinery have been proposed to play a role in LD biogenesis but the underlying molecular mechanism remains unclear. Here, we show that when nuclear receptor co-repressor 1 (NCoR1), which inhibits the transactivation of nuclear receptors, accumulates due to autophagy suppression, LD biogenesis is blocked. Ablation of ATG7, a gene essential for autophagy, suppressed the expression of gene targets of liver X receptor (LXR), a nuclear receptor responsible for fatty acid and triglyceride synthesis in an NCoR1-dependent manner. LD biogenesis in response to fasting and after hepatectomy was hampered by the suppression of autophagy. These results indicate that autophagy controls physiological hepatosteatosis by fine-tuning NCoR1 protein levels.

cell biology↗