STED sheds insight on mitochondrial protein synthesis

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Human mitochondrial DNA encodes 13 vital polypeptides that are components of the multisubunit complexes that couple Oxidative phosphorylation (OXPHOS) complexes that are found mainly in the invaginated cristae membranes. The inner boundary membrane (IBM) contains dynamic contact sites enriched for translocases that import proteins from the cytosol.

The majority of the OXPHOS subunits are nuclear-encoded and must therefore be imported from the cytosol through the outer membrane at contact sites with the inner boundary membrane.

As the majority of OXPHOS components are imported and need to be integrated in assembly with the mtDNA-encoded components, where does intramitochondrial translation occur?

As the mitochondrially encoded components are also integral members of these complexes, where does protein synthesis occur?

Image: Section of the human mitochondrial network taken at STED nanoscopy resolution. (See Figure 1 for more details).

In this paper the authors have adapted a click chemistry-based method coupled with stimulated emission depletion nanoscopy (STED) to address these questions reporting that, in human cells in culture, the majority of mitochondrial protein synthesis is detected at the cristae membranes and is spatially separated from the sites of RNA processing and maturation.

Figure 1: Images show a section of the human mitochondrial network taken at confocal and STED nanoscopy resolution using AF594 depleted with a 775nm STED laser and AF532 depleted with a 660nm STED laser. This has proven to be a crucial image to show the submitochondrial location of newly synthesised proteins. The green rendered fluorescent signal represents newly synthesised mitochondrial protein and the magenta is an immunofluorescent antibody to a mitochondrial protein found in the inner boundary membrane of the mitochondrion (TIM23).

(Deconvolved and rendered with Huygens – www.svi.nl)

Read the full article:

Zorkau M., Albus C., Berlinguer-Palmini R., Chrzanowska-Lightowlers Z. & Lightowlers R.

High-resolution imaging reveals compartmentalization of mitochondrial protein synthesis in cultured human cells

PNAS February 9, 2021 118 (6) e2008778118; 

https://doi.org/10.1073/pnas.2008778118

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