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  • Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation.

Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation.

Development (Cambridge, England) (2020-05-08)
Agnes Cheong, Danielle Archambault, Rinat Degani, Elizabeth Iverson, Kimberly D Tremblay, Jesse Mager
ABSTRACT

Mitochondria are essential for energy production and although they have their own genome, many nuclear-encoded mitochondrial ribosomal proteins (MRPs) are required for proper function of the organelle. Although mutations in MRPs have been associated with human diseases, little is known about their role during development. Presented here are the null phenotypes for 21 nuclear-encoded mitochondrial proteins and in-depth characterization of mouse embryos mutant for the Mrp genes Mrpl3, Mrpl22, Mrpl44, Mrps18c and Mrps22 Loss of each MRP results in successful implantation and egg-cylinder formation, followed by severe developmental delay and failure to initiate gastrulation by embryonic day 7.5. The robust and similar single knockout phenotypes are somewhat surprising given there are over 70 MRPs and suggest little functional redundancy. Metabolic analysis reveals that Mrp knockout embryos produce significantly less ATP than controls, indicating compromised mitochondrial function. Histological and immunofluorescence analyses indicate abnormal organelle morphology and stalling at the G2/M checkpoint in Mrp null cells. The nearly identical pre-gastrulation phenotype observed for many different nuclear-encoded mitochondrial protein knockouts hints that distinct energy systems are crucial at specific time points during mammalian development.

MATERIALS
Product Number
Brand
Product Description

Roche
Anti-Digoxigenin-AP, Fab fragments, from sheep
Roche
DIG RNA Labeling Kit (SP6/T7), sufficient for 2 x 10 labeling reactions, kit of 1 (12 components), suitable for hybridization, suitable for Southern blotting
Sigma-Aldrich
Sheep Serum, USA origin, sterile-filtered, suitable for cell culture
Sigma-Aldrich
(−)-Tetramisole hydrochloride, ≥99% (GC)