Background: During energy starvation, cells utilize intracellular resources for survival; however, the resources used during glucose starvation are unknown. Results: In glucose-starved yeast, vacuolar hydrolysis and endocytosis promote survival whereas autophagy is dispensable. Conclusion: Vacuolar hydrolysis blocks autophagy and provides resources for survival during glucose starvation. Significance: This new survival mechanism could protect cells from starvation in many situations.

Transcription errors occur in all living cells; however, it is unknown how these errors affect cellular health. To answer this question, we monitor yeast cells that are genetically engineered to display error-prone transcription. We discover that these cells suffer from a profound loss in proteostasis, which sensitizes them to the expression of genes that are associated with protein-folding diseases in humans; thus, transcription errors represent a new molecular mechanism by which cells can acquire disease phenotypes. We further find that the error rate of transcription increases as cells age, suggesting that transcription errors affect proteostasis particularly in aging cells. Accordingly, transcription errors accelerate the aggregation of a peptide that is implicated in Alzheimer's disease, and shorten the lifespan of cells. These experiments reveal a previously unappreciated role for transcriptional fidelity in cellular health and aging.

Eisosomes are furrows of the yeast plasma membrane that are involved in the regulation of nutrient transporters and membrane stress pathways. Environmental changes affect plasma membrane tension and fluidity, which change both the eisosome structure and the localization of nutrient transporters and regulatory proteins to the eisosome.

Phosphorylated phosphatidylinositol lipids are crucial for most eukaryotes and have diverse cellular functions. The low-abundance signaling lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is critical for cellular homeostasis and adaptation to stimuli. A large complex of proteins that includes the lipid kinase Fab1/PIKfyve, dynamically regulates the levels of PI(3,5)P2. Deficiencies in PI(3,5)P2 are linked to some human diseases, especially those of the nervous system. Future studies will likely determine new, undiscovered regulatory roles of PI(3,5)P2, as well as uncover mechanistic insights into how PI(3,5)P2 contributes to normal human physiology.

Background: Protein kinase C (PKC) is a nodal regulator of cell signaling. Results: Multiple interactions between conserved regulatory domains in PKC synergistically stabilize a nanomolar affinity homodimer critical for cellular function. Conclusion: Homodimerization regulates the equilibrium between the auto-inhibited and active states of PKC␣. Significance: Multiplexed interactions between modular domains dictate PKC function.

There is an intramolecular interaction in the lipid kinase Fab1 in which the upstream CCR domain contacts the Fab1 kinase region. Selected dominant-active alleles disrupt this interaction and result in elevated PI(3,5)P2. These findings suggest a regulatory mechanism that contributes to dynamic control of cellular PI(3,5)P2 synthesis.

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Persistent truncus arteriosus (TA) is an uncommon congenital cardiovascular malformation, which comprises between 0.4% and 1% of all congenital heart defects. Occurrence of TA in siblings has been reported infrequently. Twins concordant for isolated TA appear to have been reported only once previously. In this paper, we describe dizygotic twin females who were concordant for isolated TA.