Publications by authors named "Chun-Shik Shin"

Article Synopsis
  • Proteotoxicity contributes to type 2 diabetes (T2D), with a study revealing significant accumulation of misfolded proteins in the mitochondria of human pancreatic islets in T2D patients.
  • Quantitative proteomics indicate that T2D islet protein misfolding resembles mitochondrial issues rather than those from the endoplasmic reticulum (ER), highlighting the role of the protease LonP1 and its chaperone mtHSP70 in this process.
  • Deleting LONP1 in mice leads to mitochondrial dysfunction and β cell death, while enhancing LONP1 function improves mitochondrial protein folding and β cell survival, suggesting potential new therapeutic avenues for treating T2D.
View Article and Find Full Text PDF

Most mitochondrial precursor polypeptides are imported from the cytosol into the mitochondrion, where they must efficiently undergo folding. Mitochondrial precursors are imported as unfolded polypeptides. For proteins of the mitochondrial matrix and inner membrane, two separate chaperone systems, HSP60 and mitochondrial HSP70 (mtHSP70), facilitate protein folding.

View Article and Find Full Text PDF

As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system x), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration.

View Article and Find Full Text PDF

It has been reported in various model organisms that autophagy and the target of rapamycin complex 1 (TORC1) signaling are strongly involved in eukaryotic cell aging and decreasing TORC1 activity extends longevity by an autophagy-dependent mechanism. Thus, to expand our knowledge of the regulation of eukaryotic cell aging, it is important to understand the relationship between TORC1 signaling and autophagy. Many researchers have shown that TORC1 represses autophagy under normal growth conditions, and TORC1 inactivation contributes to the upregulation of autophagy.

View Article and Find Full Text PDF

Yak1 is a member of an evolutionarily conserved family of Ser/Thr protein kinases known as dual-specificity Tyr phosphorylation-regulated kinases (DYRKs). Yak1 was originally identified as a growth antagonist, which functions downstream of Ras/PKA signalling pathway. It has been known that Yak1 is phosphorylated by PKA in vitro and is translocated to the nucleus upon nutrient deprivation.

View Article and Find Full Text PDF

The target of rapamycin (TOR) signaling pathway plays crucial roles in the regulation of eukaryotic cell growth. In Saccharomyces cerevisiae, nitrogen sources in the extracellular environment activate the TOR signaling pathway. However, the precise mechanisms underlying the regulation of TOR activity in response to extracellular nitrogen sources are poorly understood.

View Article and Find Full Text PDF