Scientists have developed a new technology for studying mitochondria

Scientists have developed new technologies to study mitochondria. This progress provides a new method to study diseases with mitochondrial damage, including Alzheimer’s disease, Parkinson’s disease and other cancers.
Scripps Institute
News on February 15, 2023
Recently, in a research report published online in the Journal of Cell Biology (JCB), scientists from Scripps Research described a new technology that can image and quantify even subtle structural changes in mitochondria, and associate these changes with other ongoing processes in cells.
The research was published in the journal of Cell Biology (the latest impact factor: 8.077) on February 14, 2023
Mitochondria not only participate in energy generation, but also participate in several other key cell functions, including cell division and cell preservation response to various types of stress. Mitochondrial dysfunction has been observed in many diseases, including Alzheimer’s disease, Parkinson’s disease and different cancers. Researchers are eager to develop treatments that can reverse these dysfunction. However, the scientific tools for studying the details of mitochondrial structure are limited.
“We now have a powerful new tool kit that can detect and quantify differences in the structure and function of mitochondria, for example, in disease and health,” said Dr. Danielle Grotjahn, senior author of the study, who is an assistant professor of the Department of Integrated Structure and Computational Biology at the Scripps Institute.
The co-first authors of the study are Dr. Benjamin Barad (postdoctoral research assistant), a member of the Grotjahn laboratory, and Dr. Michaela Medina candidate.
Mitochondria is one of many membrane-bound molecular machines or “organelles” that exist in animal and plant cells. Usually, each cell has hundreds to thousands of mitochondria. They have their own small genome, and have a unique structure, including an outer membrane and a wavy inner membrane, where key biochemical reactions occur. Scientists know that the appearance of mitochondrial structure can change greatly, which depends on what mitochondria are doing or what pressure exists in cells. Therefore, these structural changes can be very useful markers of cell status, although there is no good method to detect and quantify them so far.
In this study, Grotjahn’s team integrated a computing tool package to process imaging data from a microscopic technique called Cryo-ET, which basically uses electrons rather than light to image biological samples in three dimensions. Researchers call it the “surface morphometry toolkit”, which can draw and measure the structural units of a single mitochondrial in detail. This includes the curvature of the inner membrane and the gap between the membranes, which are the markers of all important mitochondrial and cellular events that may be useful.
Barad said: “It enables us to essentially transform the beautiful three-dimensional image of mitochondria obtained from frozen embryo transfer into sensitive and quantitative measurements. For example, we can potentially use it to help identify the detailed mechanism of disease.”
The research team showed this toolkit, which they used to map the structural details of mitochondria when cells are subjected to endoplasmic reticulum stress (a cell stress common in neurodegenerative diseases). They observed that the key structural characteristics, such as the curvature of the inner membrane or the minimum distance between the inner and outer membranes, had measurable changes under this stress.
With the success of the new toolkit and the demonstration of principle verification, Grotjahn’s laboratory will now use it to study in more detail how mitochondria respond to cell stress or other changes caused by diseases, toxins, infections and even drugs.
“For example, we can compare the effects of drugs on cell mitochondria and untreated mitochondria,” Medina said. “This method is not limited to mitochondria, but we can also use it to study other organelles in cells.”
“Quantifying organelle ultrastructure in Cryo-electron tomography using a surface morphometry pipeline” was jointly written by Benjamin Barad, Michaela Medina, Daniel Fuentes, Luke Wiseman and Danielle Grotjahn, both from Scripps Institute.
Scripps Institute, founded in 1924
reference
Source：Scripps Research
Scripps Research scientists develop new technique for studying mitochondria
Reference：
Benjamin A． Barad， Michaela Medina， Daniel Fuentes， R． Luke Wiseman， Danielle A． Grotjahn； Quantifying organellar ultrastructure in cryo－electron tomography using a surface morphometrics pipeline． J Cell Biol 3 April 2023； 222 （4）： e202204093． doi： https：／／doi．org／10．1083／jcb．202204093
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