New study reveals mechanism of human mitochondrial ribosome formation

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New study reveals mechanism of human mitochondrial ribosome formation

In a new study, at first time, researchers used cryo-electron microscopy (cryo-EM) at the Diamond Light Source Electron Bio-Imaging Centre in the UK to reveal how energy makers work in the human body Forming. These researchers are from Stockholm University, Sweden, Karolinska Institutet, National Institute of Diabetes and Digestive and Kidney Diseases, University of Miami, University of Helsinki, Finland and Newcastle University, UK.

The results of the study were published in the journal Science on February 19, 2021, with the title “Mechanism of membrane-tethered mitochondrial protein synthesis“.

New study reveals mechanism of human mitochondrial ribosome formation Picture source: Dan W. Nowakowski and Alexey Amunts.

This paper reports an in-depth understanding of the molecular mechanisms of membrane-tethered protein synthesis in human mitochondria.

This is a fundamental new understanding of how the human mitochondrial ribosome (mitoribosome) works, and could explain how mitochondria are affected by mutation and dysfunction, leading to disorders such as deafness and diseases including cancer.

Mitochondria are organelles within cells that act as tiny but powerful energy factories in our bodies. They use the oxygen we inhale and derivatives of the food we eat to generate more than 90% of their energy and thus effectively support our life.

Mitochondria are especially important in high-energy-demanding organs such as the heart, liver, muscles, and brain. For example, nearly 40 percent of each cardiomyocyte is made up of mitochondria.

Much of the energy production in mitochondria takes place in naturally evolved nanofactories integrated in specialized membranes .

These nanofactories are composed of proteins that cooperate to transport ions and electrons to generate our body’s chemical energy currency (ATP). During cell division, mitochondria must be constantly maintained, replaced, and replicated.

To solve this problem, mitochondria have their own protein-making machinery, the mitochondrial ribosome. In 2014, the first basic understanding of what the mitochondrial ribosome looked like was first.

Alexey Amunts, co-corresponding author of the paper and head of the Molecular Interaction Biology program at the Life Sciences Laboratory at Stockholm University, said:

“Seven years ago, our study of the yeast mitochondrial ribosome was called the Resolution Revolution. This new study represents yet another step forward from the previous breakthrough. Not only does it reveal in unprecedented detail How the human mitochondrial ribosome is formed and also explains the molecular mechanisms that drive the processes that fuel life in bioenergetics.”

The term Resolution Revolution was coined after the first successful determination of mitochondrial ribosome structure in the journal Science.

This represents a methodological innovation in applying cryo-EM to understand molecular structure. However, the first understanding of this structure revealed only part of the static model.

However, the mitochondrial ribosome is a flexible molecular machine that requires relative movement of its parts to function.

Thus, in the new study, the researchers used cryo-EM data acquisition at the Diamond Light Source Electron Bioimaging Center to obtain 30-fold more data, allowing them to characterize the processes involved in protein synthesis and binding to membrane adaptor proteins. Conformational changes.

Amunts added, “Our study sheds light on the molecular mechanisms of this dynamic, explains how mitochondrial ribosomes actually function to form cellular energy factories, and reveals that mitochondrial ribosomes are more flexible and active than previously thought. The discovery of intrinsic conformational changes represents a gating mechanism for the mitochondrial ribosome that has no similarities in bacterial and cytoplasmic systems. Together, these data provide molecular insights into how proteins are synthesized in human mitochondria.”

Yuriy Chaban, Principal Electron Microscopy Scientist at the Diamond Light Source Electron Bioimaging Center, commented, “At Diamond Light Source, we are pushing the limits of measurement in the physical and life sciences, and thanks to our team, we can now routinely perform measurements. The most important aspect of Alexey’s work is the interaction between the human mitochondrial ribosome and the OXA1L protein and the associated flexibility. The fact that the human mitochondrial ribosome is flexible is not novel, but the specificity associated with the OXA1L interaction The flexibility is novel. This is important for the synthesis of membrane proteins, including respiratory chain proteins. Overall, this study greatly broadens our understanding of mitochondrial ribosome function. This work in the Amunts lab The research solves another mystery about the fundamental biological processes necessary to create life as we know it.”

The sequencing of the human mitochondrial genome 40 years ago was a turning point in mitochondrial research, postulating a specific mechanism for the synthesis of mitochondrial transmembrane proteins.

In fact, this discovered gating mechanism of the human mitochondrial ribosome represents a unique phenomenon. Thus, these structural data provide us with a fundamental understanding of how bioenergetic proteins are synthesized in vivo.

References:

1.Yuzuru Itoh et al. Mechanism of membrane-tethered mitochondrial protein synthesis. Science, 2021, doi:10.1126/science.abe0763.

2.Mitochondria: New data sheds light on genesis of our body’s powerhouses. https://phys .org/news/2021-02-mitochondria-genesis-body-powerhouses.html

New study reveals mechanism of human mitochondrial ribosome formation

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