{"id":9361,"date":"2016-08-17T06:51:44","date_gmt":"2016-08-17T06:51:44","guid":{"rendered":"http:\/\/wames.org.uk\/cms-english\/?p=9361"},"modified":"2016-08-17T06:51:44","modified_gmt":"2016-08-17T06:51:44","slug":"selfish-mitochondria-implicated-in-a-variety-of-diseases","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/selfish-mitochondria-implicated-in-a-variety-of-diseases\/","title":{"rendered":"Selfish mitochondria implicated in a variety of diseases"},"content":{"rendered":"

Vanderbilt University<\/strong> press release, 12 July 2016: Selfish mitochondria implicated in a variety of diseases<\/a><\/p>\n

Mitochondrial disorders are a chameleon-like set of diseases that take\u00a0many different forms and vary widely from individual to individual.<\/p>\n

Mitochondria are special organelles found in cells that produce most of\u00a0 he chemical energy that powers cell operations. Mitochondrial\u00a0dysfunction has been associated with a wide variety of illnesses,\u00a0including autism, Alzheimer’s disease, schizophrenia, dementia,
\nParkinson’s disease, epilepsy, stroke, cancer, chronic fatigue syndrome\u00a0and cardiovascular disease.<\/p>\n

There are a number of different factors that can cause mitochondria to\u00a0misbehave. However, mutations in mitochondrial DNA (mtDNA) are known to\u00a0play an outsize role. Now, a team of researchers at Vanderbilt\u00a0University has discovered that mutant mtDNA may cause diseases by\u00a0behaving ‘selfishly’ – in a fashion that benefits them while harming
\ntheir host.<\/p>\n

The Vanderbilt researchers have identified specific molecular mechanisms\u00a0that selfish mutant mtDNA use to circumvent the molecular control\u00a0mechanisms that cells have developed to regulate mitochondrial\u00a0activities. Detailed understanding of these molecular pathways could\u00a0help researchers develop effective treatments for mitochondrial\u00a0disorders.<\/p>\n

Prevalence of mitochondria disorders<\/strong><\/p>\n

‘About one newborn in every 200 inherits a potentially pathological\u00a0mitochondrial disease which becomes manifest in about one adult out of\u00a05,000,’ said Assistant Professor of Biological Sciences Maulik Patel,\u00a0who directed the Vanderbilt researchers.<\/p>\n

Their work is described in the paper ‘Homeostatic responses regulate<\/a>\u00a0selfish mitochondrial genome dynamics in C. elegans’ published in the\u00a0July 12 issue of the journal Cell Metabolism.<\/p>\n

Team members who contributed to the study were Vanderbilt doctoral\u00a0students Bryan Gitschlag and Cait Kirby, along with Associate Professor\u00a0of Molecular Physiology and Biophysics David Samuels, Senior Research\u00a0Specialists Rama Gangula and Simon Mallal and Major E.B. Shulman,\u00a0Professor of Infectious Diseases and Inflammation at the Vanderbilt\u00a0School of Medicine.<\/p>\n

‘Once we know the mechanisms that mutant mitochondria use to evade\u00a0cellular regulation, then we can develop drugs that target these\u00a0pathways and prevent the mutations from spreading,’ said Patel.<\/p>\n

Mitochondria are a unique feature in eukaryotic cells, the types of\u00a0cells found in plants and animals. The generally accepted theory is that\u00a0mitochondria were originally independent bacteria that developed an\u00a0ability to tap highly toxic oxygen molecules as a powerful energy\u00a0source: an ability that prokaryotic cells lacked. So some prokaryotes\u00a0found ways to convert the mitochondria into an ‘endosymbiont,’ an\u00a0organism that lives within the body of another organism. According to\u00a0one popular theory, this symbiosis was so successful that it provided\u00a0the eukaryotes with the added energy they needed to begin forming
\nmulti-cellular organisms.<\/p>\n

Powerhouse of the cell<\/strong><\/p>\n

Although the self-contained mitochondria are generally known by their\u00a0role as ‘the powerhouse of the cell’ they are also involved in a number\u00a0of other cellular operations, including regulation of the cell cycle and\u00a0cell growth.<\/p>\n

One of the things that make mitochondria unique is the fact that they\u00a0managed to retain their own DNA through the endosymbiosis process. The\u00a0mitochondrial genome is extremely small compared to the massive human\u00a0genome and consists of a closed ring of 37 genes inherited solely from\u00a0the mother.<\/p>\n

The number of mtDNA copies in human cells differs widely by cell type.\u00a0For example, human blood cells don’t carry any at all while human liver\u00a0cells can house more thousands of copies apiece.<\/p>\n

In a normal cell, all the copies of mtDNA are the same. However, cells\u00a0contain molecular mechanisms that disassemble and destroy unneeded or\u00a0improperly functioning cell components, including mitochondria. As a\u00a0result, these organelles can be replicated and destroyed at a very high\u00a0rate. In the resulting mix, mutant mtDNA can arise. If they reach very\u00a0high levels they become pathogenic.<\/p>\n

Unusual properties of mitochondrial disorders<\/strong><\/p>\n

Mitochondrial disorders have some unusual properties. ‘Unlike bacterial\u00a0infections that tend to be all or nothing, mitochondrial infections can\u00a0range from zero to 100 percent,’ said Patel. ‘This makes mitochondrial\u00a0disorders multi-symptomatic, with a lot of individual differences. One\u00a0person with a mutant load of 50 percent might be symptom free while\u00a0another person with 80 percent might have severe symptoms.’ In addition,
\nmitochondrial diseases are transmitted from mother to child and, except\u00a0for developmental disorders, tend to develop late in life.<\/p>\n

Patel and his colleagues studied the nature of mitochondrial disorders\u00a0in the transparent roundworm Caenorhabditis elegans (C. elegans for\u00a0short), a widely used animal model for exploring the basic processes in\u00a0the development and behavior of multi-cellular\u00a0 0rganisms, including\u00a0humans.<\/p>\n

How mutant mtDNA evade a cell’s regulatory control mechanism<\/strong><\/p>\n

The researchers found that cells activate two specific responses to deal\u00a0with the mitochondrial dysfunction that ensues due to the presence of\u00a0mutant mtDNA. Paradoxically however, these very responses inadvertently\u00a0allow the mutant mtDNA to further propagate and proliferate.<\/p>\n

‘Viewed\u00a0from this perspective, mutant mtDNA can be thought of as selfish\u00a0entities that exploit cell’s regulatory control mechanisms for their own
\nevolutionary interests,’ said Patel.<\/p>\n

Mitochondrial genome copy number<\/strong><\/p>\n

Cells possess a way to count the number of normal mitochondrial genomes\u00a0they have. This allows them to make more mitochondrial genomes when they\u00a0need more energy. The researchers found evidence supporting co-author Samuels’ prediction that some mutant mitochondrial genomes are invisible to the cell’s counting machinery. As a result, the cells make more copies of the mutant genomes in a futile quest to reach optimal energy levels. The end result is the harmful over-production of mutant copies.<\/p>\n

Mitochondrial unfolded protein response<\/strong><\/p>\n

Cells continuously monitor the health status of their mitochondria. When they detect mitochondrial dysfunction, the cells attempt to repair the problem with a procedure called the mitochondrial unfolded protein response. In addition to alleviating the dysfunction inside mitochondria, the procedure protects them from being destroyed by the cell’s disassembly mechanisms. The researchers found evidence that some mutant mitochondria can activate this response, which causes the cell to tolerate their presence and allows the mutant mtDNA to proliferate.<\/p>\n

‘These are both cases where the mutant mitochondrial genomes exploit cellular defenses for their own ‘selfish’ interests,’ said Patel.<\/p>\n","protected":false},"excerpt":{"rendered":"

Vanderbilt University press release, 12 July 2016: Selfish mitochondria implicated in a variety of diseases Mitochondrial disorders are a chameleon-like set of diseases that take\u00a0many different forms and vary widely from individual to individual. Mitochondria are special organelles found in … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[2812,3028,3026,3029],"class_list":["post-9361","post","type-post","status-publish","format-standard","hentry","category-news","tag-mtdna","tag-prof-maulik-patel","tag-selfish-mitochondria","tag-vanderbilt-university"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-2qZ","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/9361","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=9361"}],"version-history":[{"count":3,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/9361\/revisions"}],"predecessor-version":[{"id":9421,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/9361\/revisions\/9421"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=9361"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=9361"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=9361"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}