Symmetric arrangement of mitochondria:plasma membrane contacts between adjacent photoreceptor cells regulated by Opa1

Abstract

<jats:p>Mitochondria are known to play an essential role in photoreceptor function and survival that enables normal vision. Within photoreceptors, mitochondria are elongated and extend most of the inner-segment length, where they supply energy for protein synthesis and the phototransduction machinery in the outer segment, as well as acting as a calcium store. Here, we examined the arrangement of the mitochondria within the inner segment in detail using three-dimensional (3D) electron microscopy techniques and show they are tethered to the plasma membrane in a highly specialized arrangement. Remarkably, mitochondria and their cristae openings align with those of neighboring inner segments. The pathway by which photoreceptors meet their high energy demands is not fully understood. We propose this to be a mechanism to share metabolites and assist in maintaining homeostasis across the photoreceptor cell layer. In the extracellular space between photoreceptors, Müller glial processes were identified. Due to the often close proximity to the inner-segment mitochondria, they may, too, play a role in the inner-segment mitochondrial arrangement as well as metabolite shuttling. OPA1 is an important factor in mitochondrial homeostasis, including cristae remodeling; therefore, we examined the photoreceptors of a heterozygous<jats:italic>Opa1</jats:italic>knockout mouse model. The cristae structure in the<jats:italic>Opa1</jats:italic><jats:sup><jats:italic>+/−</jats:italic></jats:sup>photoreceptors was not greatly affected, but the mitochondria were enlarged and had reduced alignment to neighboring inner-segment mitochondria. This indicates the importance of key regulators in maintaining this specialized photoreceptor mitochondrial arrangement.</jats:p>

The 3D organisation of mitochondria in primate photoreceptors

“…The closeness and extent of the association of the cortical mitochondria with the plasma membrane suggests that some kind of contact site is formed between the mitochondrion outer membrane and the plasma membrane. This may be of the form identified in mouse rod photoreceptors 33 . We identified little evidence of the trans-cellular mitochondrial alignment described in mouse, the photoreceptors being mostly too far apart to allow apposition of such membranes.…”

The 3D Organisation of Mitochondria in Primate Photoreceptors

“…The closeness and extent of the association of the cortical mitochondria with the plasma membrane suggests that some kind of contact site is formed between the mitochondrion outer membrane and the plasma membrane. This may be of the form identi ed in mouse rod photoreceptors 34 . We identi ed little evidence of the trans-cellular mitochondrial alignment described in mouse, the photoreceptors being mostly too far apart to allow apposition of such membranes.…”

Watching synchronous mitochondrial respiration in the retina and its instability in a mouse model of macular degeneration

“…Recently, it has been shown that there is a close spatial association between some mitochondria and the plasma membrane in mouse photoreceptor inner segments (IS). Further, some display alignment with their neighbors in adjacent cells across the membranes and there are visible tethers between them at relatively consistent distances that appear to connect them even though they are in different cells 43 . This may suggest trans-cellular mitochondrial communication that could be the structural basis for the synchronized oscillations we reveal here.…”