Interaction of mitochondria and lysosomes key in Parkinson's disease

The Scientific committee would like to share this excellent article written by Soojin Kim and al. on Interaction of mitochondria and lysosomes key in Parkinson's disease.

 Credit: Northwestern University

The Scope is: Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. In this study, we demonstrate that mitochondria-lysosome contacts can dynamically form in the soma, axons, and dendrites of human neurons, allowing for their bidirectional crosstalk.

The demonstaration is: That M–L contact sites dynamically form in human neurons, and further investigates their role in neurons from patients with GBA1-linked PD. We found that loss of lysosomal GCase enzymatic activity in PD patient-derived dopaminergic neurons led to prolonged M–L contact tethering dynamics due to defective contact untethering machinery, and resulted in misregulated axonal distribution of mitochondria and decreased ATP levels.

DOI: 10.1038/s41467-021-22113-3

How mitochondria make the cut

 https://selfhacked.com/blog/mitochondria/

Mitochondria either split in half to multiply within the cell, or cut off their ends to get rid of damaged material. That's the take-away message from EPFL biophysicists in their latest research investigating mitochondrial fission. It's a major departure from the classical textbook explanation of the life cycle of this well-known organelle, the powerhouse of the cell.

DOI: 10.1038/s41586-021-03510-6

Authors: Tatjana Kleele, Timo Rey, Julius Winter, Sofia Zaganelli, Dora Mahecic, Hélène Perreten Lambert, Francesco Paolo Ruberto, Mohamed Nemir, Timothy Wai, Thierry Pedrazzini & Suliana Manley

Mitochondrial enzyme found to block cell death pathway points to new cancer treatment strategy

The Scientific Committee of the World Mitochondria Society would like to share this article by Chao Mao and al. on Mitochondrial enzyme found to block cell death pathway points to new cancer treatment strategy.

Credit: CC0 Public Domain

The Scope is: The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) plays an important and previously unknown role in blocking a form of cell death called ferroptosis, according to a new study by researchers at The University of Texas MD Anderson Cancer Center. Preclinical findings suggest that targeting DHODH can restore ferroptosis-driven cell death, pointing to new therapeutic strategies that may be used to induce ferroptosis and inhibit tumor growth.

To conclude: In GPX4-low cancers, brequinar effectively induced ferroptosis and suppressed tumor growth, but the effects were not seen in GPX4-high cancers. However, the combination of brequinar and sulfasalazine, an FDA-approved ferroptosis inducer, resulted in a synergistic effect to overcome high GPX4 expression and to block tumor growth.

DOI: 10.1038/s41586-021-03539-7

One in Five Brain Cancers Fueled by Overactive Mitochondria

A new study(link is external and opens in a new window) has found that up to 20% of glioblastomas—an aggressive brain cancer—are fueled by overactive mitochondria and may be treatable with drugs currently in clinical trials.

Mitochondria are responsible for creating the energy that fuels all cells. Though they are usually less efficient at producing energy in cancer, tumor cells in this newly identified type of glioblastoma rely on the extra energy provided by overactive mitochondria to survive.

The study, by cancer scientists at Columbia University’s Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, was published online Jan. 11 in Nature Cancer(link is external and opens in a new window).

The study also found that drugs that inhibit mitochondria—including a currently available drug and an experimental compound that are being tested in clinical trials—had a powerful anti-tumor effect on human brain cancer cells with overactive mitochondria. (Follow-up, unpublished work found that the same drugs are also active against mitochondrial tumors in glioblastomas growing in mice).

Such drugs are being tested in patients who have a rare gene fusion—previously discovered by the same researchers—that also sends mitochondria into overdrive.

“We can now expand these clinical trials to a much larger group of patients, because we can identify patients with mitochondria-driven tumors, regardless of the underlying genetics,” says Antonio Iavarone, MD, professor of neurology, who led the study with Anna Lasorella, MD, professor of pediatrics. Both are members of Columbia’s Institute for Cancer Genetics(link is external and opens in a new window).

Read more here: https://www.cuimc.columbia.edu/news/one-five-brain-cancers-fueled-overactive-mitochondria