ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones.

Takamasa Masuda,Satoru Kawamura,Yasutaka Wada

doi:10.1038/srep22360

Abstract

Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria.

Highlights

Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth
At higher magnification under a light microscope, ES1-immunopositive signals were weaker at apical and central regions of the cone ellipsoids where mega-mitochondria are located (Supplementary Fig. S2). This is probably due to low antibody permeability to access the inside of mega-mitochondria because similar immunostaining pattern was observed with antibody against mitochondrial aspartate aminotransferase, a mitochondrial matrix-marker protein (Supplementary Fig. S2)
The size of individual mitochondria has recently been known to be regulated by a dynamic equilibrium between fusion and fission

Summary

Introduction

Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria Both rod and cone photoreceptor cells are high energy-consuming cells[1,2,3]. Orthologues of ES1 are conserved across species from E. coli (σ cross-reacting protein 27A) to human, with strong similarities ranging from 77 to 81%, implying their significant physiological role(s) conserved among prokaryote and eukaryotic mitochondria[13] These facts together with a previous finding in our laboratory that ES1 is highly abundant compared with any other proteins in purified carp cones consisting of outer segment plus ellipsoid Our data strongly suggested that ES1 supports energy production via mitochondrial enlargement

Methods

Results

Conclusion