Active Ras2 in mitochondria promotes regulated cell death in a cAMP/PKA pathway-dependent manner in budding yeast.

Barbara Bonomelli, Stefano Busti, Enzo Martegani, Sonia Colombo

FEBS letters 2023 Jan

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Previously, we showed that an aberrant accumulation of activated Ras in mitochondria correlates with an increase in apoptosis. In this article, we show that lack of trehalose-6P-synthase, known to trigger apoptosis in Saccharomyces cerevisiae, induces localization of active Ras proteins in mitochondria, confirming the above-mentioned correlation. Next, by characterizing the ras1Δ and ras2Δ mutants, we show that active Ras2 proteins, which accumulate in the mitochondria following addition of acetic acid (a pro-apoptotic stimulus), are likely the GTPases involved in regulated cell death, while active Ras1 proteins, constitutively localized in mitochondria, might be involved in a pro-survival molecular machinery. Finally, by characterizing the gpa2Δ and cyr1Δ mutants, in which the cAMP/PKA pathway is compromised, we show that active mitochondrial Ras proteins promote apoptosis through the cAMP/PKA pathway. © 2022 Federation of European Biochemical Societies.

Citation

Barbara Bonomelli, Stefano Busti, Enzo Martegani, Sonia Colombo. Active Ras2 in mitochondria promotes regulated cell death in a cAMP/PKA pathway-dependent manner in budding yeast. FEBS letters. 2023 Jan;597(2):298-308