PgmNr Y526: The respiration/fermentation switch in yeast requires protein aggregation.

Authors:
Kobi Simpson-Lavy 1 ; Mark Johnston 2 ; Martin Kupiec 1


Institutes
1) Tel Aviv University, Tel Aviv, IL; 2) University of Colorado-Denver, Aurora, CO, USA.


Keyword: Cell Cycle/Growth Control/Metabolism

Abstract:

Amyloidogenic proteins (such as Huntingtin) and prions are sequestered under stress conditions or their overexpression into special particles/compartments called IPOD and JUNQ. This process involves the chaperones Hsp104, Btn2 and Cur1. Utilization of non-fermentable carbon sources requires the activity of the Snf1 protein kinase. Snf1 is active in the absence of glucose and regulates the expression and activity of proteins involved in respiration. We have identified two new regulators of Snf1 activity in S. cerevisiae. These new regulators (Vhs1 and Sip5) control the aggregation of the Snf1 activator Std1 in response to glucose via the asparagine-rich region of Std1. Interestingly, aggregated Std1 localizes to the IPOD under ambient conditions and this utilizes the same chaperones used by amyloidogenic proteins and prions under pathological or stressful conditions. Thus, amyloidogenic aggregation is a normal, non-pathological physiological state that can be used to regulate central metabolic processes. These results shed light on the evolutionary role of protein aggregation in eukaryotes and have implications for our understanding of cancer and neurodegenerative diseases.



Yeast Database Genetic Index
1. gene symbol: Snf1; systematic name: YDR477W
2. gene symbol: Std1; systematic name: YOR047C
3. gene symbol: Sip5; systematic name: YMR140W
4. gene symbol: Vhs1; systematic name: YDR247W
5. gene symbol: Hsp104; systematic name: YLL026W
6. gene symbol: Btn2; systematic name: YGR142W
7. gene symbol: Cur1; systematic name: YPR158W