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

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.

Differential gene expression in chicken primary B cells infected ex vivo with attenuated and very virulent strains of infectious bursal disease virus (IBDV)

“…In addition, LOC422305 and MCOLN2, found to be significantly downregulated in cells infected with D78 relative to those infected with UK661, were also included in this group, making a total of 18 genes. The LOC422305 gene encodes the mitochondrial-like ES1 protein [21], and the MCOLN2 gene encodes the ion channel TRPML2 [22] that has been reported to enhance the replication of yellow fever and dengue viruses [23,24]. The other three groups comprised the 53 genes that were transcribed to a higher level in D78-infected cells relative to mock-infected cells, as well as the two genes that were significantly up-regulated by infection with D78 relative to infection with UK661 (HBG2 and HSP25), making a total of 55 genes.…”

Daily mitochondrial dynamics in cone photoreceptors

“…There are hundreds of mitochondria in zebrafish cones packed tightly between the nucleus and outer segment. Previous studies revealed that these mitochondria are heterogeneous (Kim et al 2005;Tarboush et al 2014;Masuda et al 2016). In this report we quantified the differences in mitochondrial number, size, complexity and 3-D distribution in zebrafish cone subtypes.…”

“…Like cones in other species (T. Ishikawa & Yamada 1969;Knabe & Kuhn 1996) zebrafish cones form megamitochondria, maintained by the enlargement factor ES1 (Masuda et al 2016;Utsumi et al 2020). While we did not detect daily changes to es1 mRNA transcripts in whole retinas, we observed a small population of juxtaposed megamitochondria in all cones throughout the day.…”

“…Transcripts encoding the mitochondrial fusion protein mfn2 rise in the morning ( Figure 4C, top), suggesting fusion could mediate the corresponding decrease in mitochondrial number. No significant changes were detected in the zebrafish cone mitochondrial enlarging factor es1 (Masuda et al 2016) (Figure 4C, middle). Overall we found no striking differences in transcript levels between LD and DD groups, indicating that expression of mitochondrial biogenesis genes is regulated primarily by the circadian clock.…”

SS-31 Reverses Mitochondrial Fragmentation in Fibroblasts from Patients with DCMA, a Mitochondrial Cardiomyopathy

“…Implicated genes of particular note included DNAJC19 and those involved in oxidative stress (GSTM1) and mitochondrial biogenesis (GATD3A) (31,32).…”