PgmNr D207: Mitochondrial-nuclear incompatibility during oogenesis causes embryonic lethality.

Authors:
C. Zhang 1 ; K. Montooth 2 ; B. Calvi 1


Institutes
1) Indiana University, Bloomington, IN; 2) University of Nebraska-Lincoln,Lincoln, NE.


Keyword: homeostasis & stress

Abstract:

Female reproduction is strongly affected by age, nutrition and metabolic homeostasis. There is increasing evidence that age-related female infertility is associated with reduced mitochondrial function. Although mitochondria have their own genomes, ~1500 nuclear-encoded gene products are transported into mitochondria and are required for mitochondrial function. Mutations in either these nuclear or mitochondria-encoded genes are known causes of a number of human mitochondrial diseases. It is less clear, however, whether mitochondrial diseases can result from specific incompatibilities between the nuclear and mitochondrial genomes. 

Here, we use a previously established mito-nuclear incompatible Drosophila model to investigate its impact on female fertility. The (simw501); OreR mito-nuclear genotype carries mitochondria from D. simulans in a D. melanogaster OreR nuclear background. It was previously shown that a mito-nuclear incompatibility in this strain results in developmental delay, defective muscle function, and reduced oxidative phosphorylation. The basis for this mito-nuclear incompatibility are polymorphisms in the mitochondria-encoded tyrosyl-tRNA and the nuclear-encoded mitochondrial tyrosyl-tRNA synthetase (Aats-tyr-m or Aatm) genes. We now show that this incompatible (simw501); OreR strain has severe oogenesis defects, including death of germline stem cells and cystocytes, and egg chamber degeneration, which together result in reduced egg production. In addition, these strains have a strict temperature-sensitive maternal-effect embryonic lethality that is completely dependent on the developmental temperature of the mother. The temperature sensitive period in the mother is during late 3rd instar / pupation, and is not reversible by shifting the temperature of adult females. These last observations suggest that continued embryonic lethality results from some type of maternal metabolic memory. Our findings show that maternal mito-nuclear incompatibility has severe consequences for oogenesis and embryonic survival. More broadly, our results raise the possibility that mito-nuclear incompatibility could cause female infertility in humans.



Flybase Genetic Index:
1. FlyBase gene symbol: Aats-tyr-m; FBgn: FBgn0035064