Mitochondrial haplotypes influence metabolic traits across bovine inter- and intra-species cybrids

Jikun Wang,Xingbo Zhao,Tao Yin,Langqing Liu,Minghua Kong,Hai Xiang

doi:10.1038/s41598-017-04457-3

Abstract

In bovine species, mitochondrial DNA polymorphisms and their correlation to productive or reproductive performances have been widely reported across breeds and individuals. However, experimental evidence of this correlation has never been provided. In order to identify differences among bovine mtDNA haplotypes, transmitochondrial cybrids were generated, with the nucleus from MAC-T cell line, derived from a Holstein dairy cow (Bos taurus) and mitochondria from either primary cell line derived from a domestic Chinese native beef Luxi cattle breed or central Asian domestic yak (Bos grunniens). Yak primary cells illustrated a stronger metabolic capacity than that of Luxi. However, all yak cybrid parameters illustrated a drop in relative yak mtDNA compared to Luxi mtDNA, in line with a mitonuclear imbalance in yak interspecies cybrid. Luxi has 250 divergent variations relative to the mitogenome of Holsteins. In cybrids there were generally higher rates of oxygen consumption (OCR) and extracellular acidification (ECAR), and lower mRNA expression levels of nuclear-encoded mitochondrial genes, potentially reflecting active energy metabolism and cellular stress resistance. The results demonstrate that functional differences exist between bovine cybrid cells. While cybrid viability was similar between Holstein and Luxi breeds, the mitonuclear mismatch caused a marked metabolic dysfunction in cattle:yak cybrid species.

Highlights

The mitochondrion is a complex organelle that houses essential pathways involved in energy metabolism, ion homeostasis, signal transduction and apoptosis[1]
Cybrid cells (C0+C0, C0+C1 and C0+Y) were sequenced, and the mitogenome sequence of each cybrid cell was consistent with its mitochondria donor
Dynamic properties associated with energy metabolism in yak primary cell culture were comparable to living yaks

Summary

Introduction

The mitochondrion is a complex organelle that houses essential pathways involved in energy metabolism, ion homeostasis, signal transduction and apoptosis[1] Both mitochondrial and nuclear genomes must be highly compatible to maintain the structural and biochemical properties for OXPHOS function[2]. Because of confounding variations in the nuclear genome, epigenetic phenomena and environmental factors, it was difficult to evaluate the contribution that mtDNA variants might have to complex trait characteristics. We chose the well-characterized bovine mammary alveolar cell line (MAC-T, from a Holstein cow) as the nucleus donor, and somatic cell lines from a yak (Bos grunniens) and a Chinese native cattle, Luxi (Bos taurus) as mitochondria donors, to generate bovine intra- and inter-species cybrids. This study provides the first evidence detailing mtDNA effects using transmitochondrial cells across intra- and inter-bovine species

Objectives

Methods

Results

Conclusion