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Las vesículas que contienen P impulsan las etapas tardías de la división mitocondrial

Shun Nagashima¹, Luis-Carlos Tábara¹, Lisa Tilokani¹

¹Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.

Science (New York, N.Y.)

|March 21, 2020

Resumen

El fosfatidilinositol 4-fosfato (PI(4) en las vesículas de Golgi impulsa la división mitocondrial aguas abajo de la proteína relacionada con la dinamina-1 (Drp1). La pérdida de Arf1 o PI(4) KIIIβ afecta la generación de PI(4) P, lo que lleva a defectos en la red mitocondrial.

Área de la Ciencia:

Biología celular
Biología molecular
La bioquímica

Sus antecedentes:

La plasticidad mitocondrial, regulada por la división mitocondrial, es crucial para el destino celular.
La proteína-1 relacionada con la dinamina (Drp1) media la división mitocondrial en los sitios de contacto del retículo endoplasmático (ER), pero los mecanismos de escisión final siguen siendo elusivos.

Objetivo del estudio:

Para aclarar los mecanismos moleculares que rigen los pasos finales de la división mitocondrial.
Investigar el papel del fosfatidilinositol 4-fosfato en la escisión mitocondrial.

Principales métodos:

Se utilizaron líneas celulares de mamíferos para estudiar la división mitocondrial.
Se investigó la función del factor de ribosilación ADP 1 (Arf1) y la fosfatidilinositol 4-cinasa IIIβ (PI(4) KIIIβ) en la generación de PI(4) P.
Morfología mitocondrial observada y sitios de constricción utilizando microscopía.

Principales resultados:

Se reclutaron microdomínios de PI(4) P en las vesículas de la red trans-Golgi (TGN) a los sitios de contacto mitocondria-ER.
El reclutamiento de vesículas que contienen PI ((4) P promovió la división mitocondrial aguas abajo de Drp1.
La pérdida de Arf1 o PI(4) KIIIβ abolió la generación de PI(4) P, lo que resultó en redes mitocondriales hiperfusionadas y sitios de constricción extendidos.

Conclusiones:

Las vesículas TGN-PI ((4) P juegan un papel crítico en el desencadenamiento de los eventos finales de la escisión mitocondrial.
La vía Arf1-PI ((4) KIIIβ-PI ((4) P es esencial para regular la división mitocondrial en los sitios de contacto de ER.

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