Scientists from Heinrich Heine University Düsseldorf and University of California Los Angeles recently discovered that cristae – structures formed by the inner covering of mitochondria – keep remodelling continuously. The team led by Prof. Andreas S. Reichert made this discovery by seeing live cells using a high-end technique in microscopy. This technique, called stimulated emission depletion (STED) super-resolution nanoscopy, enables one to see details of an organelle in the cell – of the size of 50 nm (about 1000 times smaller than a speck of dust). The study was published in the journal EMBO Reports.     

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STED nanoscopy images showing cristae remodelling 

Mitochondria are organelles in the cell popularly known as the powerhouse of the cell. They form a dynamic network, change their shape, fuse or split. As for their structure, mitochondria have two membranes covering them – the outer membrane and the inner membrane. The inner membrane folds inward to form structures called cristae (sing. crista), on which many important proteins reside. These proteins include ATP synthase – the machine that makes ATP, the energy currency of the cell. Curved, circular or pore-like structures called crista junctions separate the cristae and the rest of the inner membrane.

Other scientists have shown that abnormal or altered cristae in diseases like cancer, diabetes and neurodegeneration. In normal conditions, however, cristae are thought to be static. Scientists from Heinrich Heine University Düsseldorf and University of California Los Angeles led by Prof. Reichert have now found that the cristae membrane and crista junctions reshape continuously. They also found that a protein complex called the mitochondrial contact site and cristae organizing system (MICOS) orchestrate these remodelling events.

 “Prof. Reichert’s lab has been working on the mechanisms of cristae remodelling. We were working on the function of MICOS complex located at the crista junctions,” Dr Arun Kumar Kondadi, one of the first authors of the paper, said. But one could never investigate if the cristae were dynamic or not as there was no technique that enabled researchers to see the details inside an organelle. “For more than half a century, it was rather assumed that cristae are static,” Dr Kondadi said. “Super-resolution microscopy techniques paved us the way to discover something really fascinating.”

In this study, using STED super-resolution nanoscopy, researchers have shown that adjacent crista junctions come together and separate from each other reversibly in human cells. For this, the researchers stained cristae membranes using dyes (or marked proteins present on the inner membrane of mitochondria) and observed how the cristae remodel using STED super-resolution nanoscopy. These experiments showed that cristae undergo membrane remodelling continuously.

According to Prof. Reichert, as quoted in the Press Release from Heinrich Heine University, the observations of this study lead us to a new model – Cristae Fission–Fusion (CriFF) model – that cristae can stay as isolated vesicles within mitochondria and then re-fuse with the inner membrane after fission. The study shows that this fusion is carried out by the MICOS complex. MIC60 – one of the proteins of the complex – initiates the process and marks the crista junction. It then recruits other proteins of the MICOS complex (MIC10, MIC13, MIC19, MIC25, MIC26 and MIC27) and completes the assembly. These crista junctions now become the sites from where cristae form. These junctions keep merging and splitting. The cristae could, therefore, pinch off from these junctions and come back to the same junction or another.

This study has opened a new field in research where one could investigate how a mitochondrion ensures quality control within itself. For all we know now, remodelling and reshaping of mitochondria in a cell can control the fate of the cell. This study has gone one step ahead to show how structures within the mitochondrial remodel continuously. How these events inside mitochondria can affect the mitochondria, and how this impact on mitochondria can influence the cell will be interesting to study.

Read the full paper here

Image Courtesy & Article Source: EMBO Reports

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