Daily mitochondrial dynamics in cone photoreceptors

Giarmarco, Michelle M.; Brock, Daniel C; Robbings, Brian M.; Cleghorn, Whitney M.; Tsantilas, Kristine; Kuch, Kellie C.; Ge, William; Rutter, Kaitlyn M.; Parker, Edward D; Hurley, James B.; Brockerhoff, Susan E.

doi:10.1073/pnas.2007827117

“…Our observations of mitochondrial expulsion of electron-dense aggregates from the photoreceptor are broadly in agreement with those described in zebra sh 42 . In this elegant paper the authors refer to similar structures they identi ed in mouse.…”

Section: Discussionsupporting

confidence: 91%

The 3D Organisation of Mitochondria in Primate Photoreceptors

Hayes

¹

,

Tracey‐White

²

,

Kam

³

et al. 2021

Preprint

View full text Add to dashboard Cite

Vertebrate photoreceptors contain large numbers of closely-packed mitochondria which sustain the high metabolic demands of these cells. These mitochondria populations are dynamic and undergo fusion and fission events. This activity serves to maintain the population in a healthy state. In the event of mitochondrial damage, sub-domains, or indeed whole mitochondria, can be degraded and population homeostasis achieved. If this process is overwhelmed cell death may result. Death of photoreceptors contributes to loss of vision in aging individuals and is associated with many eye diseases. In this study we used serial block face scanning electron microscopy of adult (Macaca fascicularis) retinae to examine the 3D structure of mitochondria in rod and cone photoreceptors. Healthy-looking photoreceptors contain mitochondria with a range of shapes which are associated with different regions of the cell. In some photoreceptors we observe mitochondrial swelling and other changes we associate with stress or degeneration of the cell. In both rods and cones we identify elongated domains of mitochondria with densely-packed normal cristae associated with photoreceptor ciliary rootlet bundles. We observe mitochondrial fission and mitochondrion fragments localised to these domains. Swollen mitochondria with few intact cristae are located towards the periphery of the photoreceptor inner-segment in rods, whilst they are found throughout the cell in cones. Swollen mitochondria exhibit sites on the mitochondrial inner membrane which have undergone complex invagination resulting in membranous, electron-dense aggregates. Membrane contact occurs between the mitochondrion and the photoreceptor plasma membrane in the vicinity of these aggregates, and a series of subsequent membrane fusions results in expulsion of the mitochondrial aggregate from the photoreceptor. These events are primarily associated with rods, likely reflecting the ageing mechanism in primates where many rods die but cones do not. Possible consequences of this atypical mitochondrial degradation are discussed.

show abstract

“…Our observations of mitochondrial expulsion of electron-dense aggregates from the photoreceptor are broadly in agreement with those described in zebrafish 41 . In this elegant paper the authors refer to similar structures they identified in mouse.…”

Section: Discussionsupporting

confidence: 91%

The 3D organisation of mitochondria in primate photoreceptors

Hayes

¹

,

Tracey‐White

²

,

Kam

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Vertebrate photoreceptors contain large numbers of closely-packed mitochondria which sustain the high metabolic demands of these cells. These mitochondria populations are dynamic and undergo fusion and fission events. This activity serves to maintain the population in a healthy state. In the event of mitochondrial damage, sub-domains, or indeed whole mitochondria, can be degraded and population homeostasis achieved. If this process is overwhelmed cell death may result. Death of photoreceptors contributes to loss of vision in aging individuals and is associated with many eye diseases. In this study we used serial block face scanning electron microscopy of adult (Macaca fascicularis) retinae to examine the 3D structure of mitochondria in rod and cone photoreceptors. Healthy-looking photoreceptors contain mitochondria with a range of shapes which are associated with different regions of the cell. In some photoreceptors we observe mitochondrial swelling and other changes we associate with stress or degeneration of the cell. In both rods and cones we identify elongated domains of mitochondria with densely-packed normal cristae associated with photoreceptor ciliary rootlet bundles. We observe mitochondrial fission and mitochondrion fragments localised to these domains. Swollen mitochondria with few intact cristae are located towards the periphery of the photoreceptor inner-segment in rods, whilst they are found throughout the cell in cones. Swollen mitochondria exhibit sites on the mitochondrial inner membrane which have undergone complex invagination resulting in membranous, electron-dense aggregates. Membrane contact occurs between the mitochondrion and the photoreceptor plasma membrane in the vicinity of these aggregates, and a series of subsequent membrane fusions results in expulsion of the mitochondrial aggregate from the photoreceptor. These events are primarily associated with rods, likely reflecting the ageing mechanism in primates where many rods die but cones do not. Possible consequences of this atypical mitochondrial degradation are discussed.

show abstract

“…Extraction of RNA, cDNA synthesis, and qRT-PCR amplification were conducted, as previously described using TATA-box binding protein as a reference gene ( 37 , 60 ). The primers are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

A highly conserved zebrafish IMPDH retinal isoform produces the majority of guanine and forms dynamic protein filaments in photoreceptor cells

Cleghorn

¹

,

Burrell

²

,

Giarmarco

³

et al. 2022

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Inosine monophosphate dehydrogenase (IMPDH) is a key regulatory enzyme in the de novo synthesis of the purine base guanine. Dominant mutations in human IMPDH1 cause photoreceptor degeneration for reasons that are unknown. Here, we sought to provide some foundational information on Impdh1a in the zebrafish retina. We found that in zebrafish, gene subfunctionalization due to ancestral duplication resulted in a predominant retinal variant expressed exclusively in rod and cone photoreceptors. This variant is structurally and functionally similar to the human IMPDH1 retinal variant and shares a reduced sensitivity to GTP-mediated inhibition. We also demonstrated that Impdh1a forms prominent protein filaments in vitro and in vivo in both rod and cone photoreceptor cell bodies, synapses, and to a lesser degree, in outer segments. These filaments changed length and cellular distribution throughout the day consistent with diurnal changes in both mRNA and protein levels. The loss of Impdh1a resulted in a substantial reduction of guanine levels, although cellular morphology and cGMP levels remained normal. Our findings demonstrate a significant role for IMPDH1 in photoreceptor guanine production and provide fundamental new information on the details of this protein in the zebrafish retina.

show abstract

Daily mitochondrial dynamics in cone photoreceptors

Cited by 46 publications

References 113 publications

The 3D Organisation of Mitochondria in Primate Photoreceptors

The 3D Organisation of Mitochondria in Primate Photoreceptors

The 3D organisation of mitochondria in primate photoreceptors

A highly conserved zebrafish IMPDH retinal isoform produces the majority of guanine and forms dynamic protein filaments in photoreceptor cells

Contact Info

Product

Resources

About