News

16th World Congress on Targeting Mitochondria | 2025

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.

interactiono

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

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.

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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

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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).

How mitochondria make the cut

bigstock-173416106-1 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

Mitochondria found to be protected by ketogenesis

Mitochondria News

Ketone bodies are generally an alternative energy source during starvation, but in newborns, ketogenesis is active regardless of nutritional status. In a recent study from Kumamoto University (Japan), researchers analyzed the effects of ketogenesis in mice and found that it has a protective effect on cells by maintaining the function of mitochondria. They expect that this effect can be used in future therapies for protecting mitochondria and organs.

Ketones, along with glucose and fatty acids, are metabolites used as energy sources. In particular, ketones are known to be an alternative energy source during periods of fasting or starvation. However, ketogenesis is known to be active in the neonatal period regardless of the number of calories consumed during nursing, and role it plays in newborns is not well understood.

To search for answers, researchers generated ketogenesis-deficient mice that lacked the gene for HMG-CoA Synthase 2 (HMGCS2), an important enzyme ketogenesis. Their analysis showed that, in the absence of ketone bodies, the mice developed a severely fatty liver during the neonatal period.

Focusing on the mitochondria, they showed that enzymatic reactions in the mitochondria, mainly the Krebs cycle, were impaired. Nutrients are converted to acetyl CoA during the Krebs cycle, which is then converted to citric acid and seven other acids to produce energy. In the search for the cause of the dysfunction, researchers confirmed that the accumulation of the substrate acetyl CoA (due to insufficient ketogenesis) impairs the functions of proteins in the mitochondria by adding excessive acetylation.

"During a rapid increase in fatty acid intake with postnatal nursing, active ketogenesis under normal conditions has a protective effect by preventing excessive acetylation of mitochondrial proteins and maintaining mitochondrial function," said study leader Dr. Yuichiro Arima. "We believe that this result will be used in therapeutic applications for mitochondrial and organ protection in the future."

News source: www.sciencedaily.com

Article source: Yuichiro Arima, Yoshiko Nakagawa, Toru Takeo, Toshifumi Ishida, Toshihiro Yamada, Shinjiro Hino, Mitsuyoshi Nakao, Sanshiro Hanada, Terumasa Umemoto, Toshio Suda, Tetsushi Sakuma, Takashi Yamamoto, Takehisa Watanabe, Katsuya Nagaoka, Yasuhito Tanaka, Yumiko K. Kawamura, Kazuo Tonami, Hiroki Kurihara, Yoshifumi Sato, Kazuya Yamagata, Taishi Nakamura, Satoshi Araki, Eiichiro Yamamoto, Yasuhiro Izumiya, Kenji Sakamoto, Koichi Kaikita, Kenichi Matsushita, Koichi Nishiyama, Naomi Nakagata, Kenichi Tsujita. Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation. Nature Metabolism, 2021; 3 (2): 196 DOI: 10.1038/s42255-021-00342-6