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Sir2 regula la autofagia selectiva en células de levadura en fase estacionaria

Ji-In Ryu¹, Juhye Jung¹, Jeong-Yoon Kim¹

¹Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.

Microbial cell (Graz, Austria)

|January 26, 2026

Resumen

El estudio revela que Sir2, una histona deacetilasa, suprime la autofagia selectiva durante la fase estacionaria de la levadura en medios ricos en nutrientes. La deleción de SIR2 activa la autofagia, afectando la degradación de orgánulos y la quiescencia celular.

Área de la Ciencia:

Biología Celular
Biología Molecular
Genética de Levaduras

Sus antecedentes:

La autofagia mantiene la homeostasis celular, especialmente durante la limitación de nutrientes.
La regulación de la autofagia durante la fase estacionaria prolongada en medios complejos es poco conocida.
Sir2 es una histona deacetilasa dependiente de NAD+ en levaduras.

Objetivo del estudio:

Investigar el papel de Sir2 en la regulación de la autofagia durante la fase estacionaria en medios complejos ricos en nutrientes.
Identificar los mecanismos por los cuales Sir2 controla la autofagia selectiva.
Comprender la contribución de Sir2 a la adaptación celular durante el estrés prolongado.

Principales métodos:

Se utilizó el procesamiento de GFP-Atg8 para medir el flujo autofágico.
Se realizó un análisis transcriptómico para evaluar los cambios en la expresión génica.
Se investigó la estabilización y fosforilación de proteínas de componentes clave de la autofagia (p. ej., Atg32).
Se emplearon estrategias de deleción génica (deleción de SIR2) en Saccharomyces cerevisiae.

Principales resultados:

La deleción de Sir2 condujo a una activación sostenida de la autofagia durante la fase estacionaria.
Sir2 inhibió selectivamente la mitofagia, la pexofagia y la vía Cvt, pero no la autofagia no selectiva.
Sir2 estabilizó Ume6, reprimiendo la transcripción de ATG8 y limitando la autofagia.
La deleción de SIR2 aumentó la estabilización de Atg32 y la mitofagia, creando un bucle de retroalimentación positiva mediado por ROS.

Conclusiones:

Sir2 es un supresor novedoso de la autofagia selectiva durante la fase estacionaria de la levadura en medios complejos.
Sir2 regula la biogénesis ribosomal y las vías de respuesta a nutrientes para la quiescencia.
El control de Sir2 sobre la degradación de orgánulos es crucial para la viabilidad bajo estrés metabólico.

Palabras clave:

Saccharomyces cerevisiae Sir2 autofagia medio complejo fase estacionaria

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