Research Articles – Page 13

Research, Research Articles

The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe

Theodora Sideri¹, Yoko Yashiroda², David A. Ellis¹, María Rodríguez-López¹, Minoru Yoshida², Mick F. Tuite³ & Jürg Bähler¹

Ctr4 exhibits multiple features diagnostic of other fungal prions and is the first example of a prion in fission yeast. These findings suggest that transmissible protein-based determinants of traits may be more widespread among fungi.

Improvement of biochemical methods of polyP quantification

Samuel Bru¹, Javier Jiménez¹, David Canadell^2,#, Joaquín Ariño², Josep Clotet¹

As the main output of this evaluation we propose a straightforward and robust procedure that can be used as gold standard protocol for cellular polyP purification and determination from unicellular organisms, thus providing consistency to measurements and facilitating inter-laboratory comparisons and biological interpretation of the results.

Bax mitochondrial relocation is linked to its phosphorylation and its interaction with Bcl-xL

David Garenne^1,2, Thibaud T. Renault^1,3, Stéphen Manon¹

The heterologous expression of Bax, and other Bcl-2 family members, in the yeast Saccharomyces cerevisiae, has proved to be a valuable reporter system to investigate the molecular mechanisms underlying their interaction with mitochondria. Our data provide the molecular basis for a model of dynamic equilibrium for Bax localization and activation, regulated both by phosphorylation and Bcl-xL.

Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae

Santiago Cavero^1,2, Esther Herruzo¹, David Ontoso^1,3 and Pedro A. San-Segundo¹

In meiotic cells, the pachytene checkpoint or meiotic recombination checkpoint is a surveillance mechanism that monitors critical processes, such as recombination and chromosome synapsis, which are essential for proper distribution of chromosomes to the meiotic progeny. We report here that Sas2-mediated acetylation of histone H4 at lysine 16 (H4K16ac) modulates meiotic checkpoint activity in response to synaptonemal complex defects. Our results reveal that proper levels of H4K16ac orchestrate this meiotic quality control mechanism and that Sir2 impinges on additional targets to fully activate the checkpoint.

The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose

Luna Laera^1,#, Nicoletta Guaragnella^1,#, Maša Ždralević^1,¶, Domenico Marzulli¹, Zhengchang Liu² and Sergio Giannattasio¹

Yeast Saccharomyces cerevisiae grown on glucose undergoes programmed cell death (PCD) induced by acetic acid (AA-PCD), but evades PCD when grown in raffinose. This is due to concomitant relief of carbon catabolite repression (CCR) and activation of mitochondrial retrograde signaling. In this work, we investigated the relationships between the RTG and CCR pathways in the modulation of AA-PCD sensitivity under glucose repression or de-repression conditions. Our data show that simultaneous mitochondrial retrograde pathway activation and SNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.

The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription

Rubin Jiao¹, Liubov Lobanova¹, Amanda Waldner¹, Anthony Fu¹, Linda Xiao¹, Troy A. Harkness¹, and Terra G. Arnason^1,2

The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.

Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets

January Weiner 3rd¹ and Taco W.A. Kooij²

In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.

VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast

Dário Trindade^1,2, Clara Pereira^3,4, Susana R. Chaves¹, Stéphen Manon², Manuela Côrte-Real¹ and Maria João Sousa¹

Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.

Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging

Andrea L. Ruetenik^1,2,3, Alejandro Ocampo^1,2,3,¶, Kai Ruan^4,5,#, Yi Zhu^4,5, Chong Li^4,6, R. Grace Zhai^1,4,5,6 and Antoni Barrientos^1,2,3,5

Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.

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Thiol trapping and metabolic redistribution of sulfur metabolites enable cells to overcome cysteine overload

March 27, 2017

In this study, researchers investigate the mechanisms for handling cysteine overload using Saccharomyces cerevisiae, finding that overexpressing the high affinity cysteine transporter, YCT1, enables yeast cells to rapidly accumulate high levels of intracellular cysteine. The study demonstrates that cells can manage potentially toxic levels of cysteine by converting it to non-reactive thiol forms and utilizing the metabolic products for cell growth.

Identification of Ftr1 and Zrt1 as iron and zinc micronutrient transceptors for activation of the PKA pathway in Saccharomyces cerevisiae

March 2, 2017

We now show that the yeast high-affinity iron transporter Ftr1 and high-affinity zinc transporter Zrt1 function as transceptors for the micronutrients iron and zinc. We show that replenishment of iron to iron-starved cells or zinc to zinc-starved cells triggers within 1-2 minutes a rapid surge in trehalase activity, a well-established PKA target.

Balanced CoQ₆ biosynthesis is required for lifespan and mitophagy in yeast

February 3, 2017

In brief, we show that, in yeast, Ptc7 modulates the adaptation to respiratory metabolism by dephosphorylating Coq7 to supply newly synthesized CoQ6, and by activating mitophagy to remove defective mitochondria at stationary phase, guaranteeing a proper CLS in yeast.

Mutational analysis of fructose-1,6-bis-phosphatase FBP1 indicates partially independent functions in gluconeogenesis and sensitivity to genotoxic stress

February 1, 2017

Our results support predicted vital roles of several fructose-1,6-bisphosphatase residues for enzymatic activity and led to the identification of residues indispensable for the MMS-sensitizing effect. Despite an overlap between these two properties, careful analysis revealed two mutations, Asn75 and His324, which decouple the enzymatic activity and the MMS-sensitizing effect, indicating two distinctive biological activities linked in this key gluconeogenesis enzyme.