{"id":6370,"date":"2020-12-25T12:04:59","date_gmt":"2020-12-25T03:04:59","guid":{"rendered":"http:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=6370"},"modified":"2022-08-26T14:47:38","modified_gmt":"2022-08-26T05:47:38","slug":"choong2020","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2020year\/choong2020","title":{"rendered":"Chi-Jing Choong, Tatsusada Okuno, Hideki Mochizuki\u226aNeurology \u226b <span>Cellular exclusion of mitochondria protects cells from damage<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2020year\/2020-choong\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><em><\/p>\n<p><span class=\"lineFrame\">Publish\u00a0<\/span> <em>Autophagy<\/em><\/p>\n<p><em>Researchers from Osaka University identify a novel mechanism by which cells turn over mitochondria and maintain cell health<\/em><\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-6362 \" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/4c91d76fc4075d5b09d799ccb1e3fc4d.png?_t=1608864800\" alt=\"\" width=\"560\" height=\"470\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/4c91d76fc4075d5b09d799ccb1e3fc4d.png 696w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/4c91d76fc4075d5b09d799ccb1e3fc4d-400x336.png 400w\" sizes=\"(max-width: 560px) 100vw, 560px\" \/><br \/>Figure 1: Defective mitochondria are eliminated by mitophagy as well as extracellular release\u3000<\/p>\n<p>&nbsp;<\/p>\n<p>Mitochondria are cellular organelles that generate most of the energy cells need to function, and thus play an important role in maintaining cell health. In a new study, researchers from Osaka University discovered a novel mechanism by which cells turn over mitochondria and contribute to cellular maintenance. They further showed how this novel pathway is involved in the development of Parkinson\u2019s disease (PD).<\/p>\n<p>Most cells in the body require mitochondria to function and survive. Various disease processes and toxic agents can harm cells by damaging mitochondria, and failure to eliminate damaged mitochondria can cause neurodegenerative diseases such as PD. Unsurprisingly, cells have a quality control system that ensures the health and function of mitochondria within cells. For a long time, it was thought that this control system would consist of mitophagy only, a process by which cells degrade damaged mitochondria and recycle their individual components to then build new mitochondria. While recent studies have shown that cells in addition have the ability to transfer mitochondria out, this process remains incompletely understood.<\/p>\n<p>\u201cThe release of mitochondria into the extracellular space is a fascinating topic, but we know very little about it,\u201d says co-author Tatsusada Okuno. \u201cThe goal of our study was to investigate to which extent cells transfer mitochondria out in response to mitochondrial stress.\u201d<\/p>\n<p>To achieve their goal, the researchers generated a cell line in which mitochondria are fluorescently labeled and thus can be investigated under a fluorescence microscope. By performing time-lapse imaging over a prolonged period of time, the researchers were able to watch the release of mitochondria in real-time. Intriguingly, they were able to show by correlative light-electron microscopy, a technique that allows cellular structures to be examined at ultra-high magnification, that mitochondria were mostly released in free form and were rarely enclosed in vesicles.<\/p>\n<p>The researchers then asked what the role of mitochondrial release might be in PD. By studying cells deficient in parkin, the protein responsible for the hereditary form of PD, they were able to show markedly increased mitochondrial release in the absence of the protein. Likewise, the blood of parkin-deficient mice contained higher levels of mitochondrial proteins, further demonstrating how the absence of parkin facilitates extracellular mitochondrial release. Most importantly, however, the researchers were able to show that cerebrospinal fluids of PD patients with a mutation in parkin that renders the protein dysfunctional contained higher levels of mitochondria, demonstrating the significance of this novel mitochondrial quality control system in the development of PD in humans.<\/p>\n<p>\u201cThese are striking results that demonstrate a novel mechanism for clearing defective mitochondria and an important role for mitochondrial homeostasis in the onset of Parkinson&#8217;s disease,\u201d says corresponding author Hideki Mochizuki. \u201cThese findings may lead to the development of new biomarkers and therapeutics.\u201d<\/p>\n<p>The article, \u201cAlternative mitochondrial quality control mediated by extracellular release\u201d was published in <em>Autophagy <\/em>at DOI: <a href=\"https:\/\/doi.org\/10.1080\/15548627.2020.1848130\">https:\/\/doi.org\/10.1080\/15548627.2020.1848130<\/a><\/p>\n<p><strong>Summary:<\/strong> Researchers from Osaka University identified mitochondrial release out of cells as a novel mechanism by which cells turn over mitochondria and maintain cell health. The researchers found that cells deficient in the protein parkin, which is responsible for the hereditary form of Parkinson\u2019s disease (PD), showed markedly increased mitochondrial release. Further, This study could help develop new biomarkers and therapeutics.<\/p>\n<p><strong>Primary keyword: <\/strong>Biology<\/p>\n<p><strong>Additional keywords: <\/strong>Biochemistry, Cell Biology, Molecular Biology<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-6365 \" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/f523dc7eb9d216d6d93339cee7e1a627-1.png?_t=1608865142\" alt=\"\" width=\"672\" height=\"511\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/f523dc7eb9d216d6d93339cee7e1a627-1.png 696w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/f523dc7eb9d216d6d93339cee7e1a627-1-400x304.png 400w\" sizes=\"(max-width: 672px) 100vw, 672px\" \/><br \/>Figure 2: Live imaging (left; red represent labeled mitochondria) and electron microscopic image (right: III, IV) of mitochondria released from PC12 cells.\u3000<\/p>\n<p>&nbsp;<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-6367 \" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/07df9963e250f92e3548b42eb8a1a89b.png?_t=1608865229\" alt=\"\" width=\"600\" height=\"456\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/07df9963e250f92e3548b42eb8a1a89b.png 696w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2020\/12\/07df9963e250f92e3548b42eb8a1a89b-400x304.png 400w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><br \/>Figure 3: Mitochondrial protein (Tom40) is markedly increased in the cerebrospinal fluid of Park2 patients.\u3000<\/p>\n<p>&nbsp;<\/p>\n<p>Title: \u201cAlternative mitochondrial quality control mediated by extracellular release\u201d<\/p>\n<p>Journal: <em>Autophagy<\/em><\/p>\n<p>Authors: Chi-Jing Choong, Tatsusada Okuno, Kensuke Ikenaka, Kousuke Baba, Hideki Hayakawa, Masato Koike, Mutsumi Yokota, Junko Doi, Keita Kakuda, Toshihide Takeuchi, Akiko Kuma, Shuhei Nakamura, Yoshitaka Nagai, Seiichi Nagano, Tamotsu Yoshimori and Hideki Mochizuki<\/p>\n<p>DOI: 10.1080\/15548627.2020.1848130<\/p>\n<p>Funded by: Japan Agency for Medical Research and Development, Japan Science and Technology Agency, Advanced Bioimaging Support<\/p>\n<p>&nbsp;<\/p>\n<p><strong>About Osaka University <\/strong><\/p>\n<p>Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan&#8217;s leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan&#8217;s most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.<\/p>\n<p>Website: https:\/\/resou.osaka-u.ac.jp\/en<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Publish\u00a0 Autophagy Researchers from Osaka University identify a novel mechanism by which cell [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":6362,"parent":5550,"menu_order":54,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/6370"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=6370"}],"version-history":[{"count":6,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/6370\/revisions"}],"predecessor-version":[{"id":7586,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/6370\/revisions\/7586"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/5550"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/6362"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=6370"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}