{"id":1717,"date":"2020-08-14T17:32:39","date_gmt":"2020-08-14T17:32:39","guid":{"rendered":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/carbohydrate-metabolism\/mitochondria\/"},"modified":"2021-09-19T16:54:07","modified_gmt":"2021-09-19T14:54:07","slug":"mitochondria","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/carbohydrate-metabolism\/mitochondria\/","title":{"rendered":"Mitochondria"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><div class=\"intro\">&#8220;The mitochondria is the powerhouse of the cell&#8221;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The following occurs within the mitochondria: <\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Citric acid cycle<\/li><li>ATP production<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Stems from the prokaryotic ancestors resulted in a double layer of membrane and circular DNA (mtDNA)<\/div><\/p>\n\n\n\n<hr class=\"wp-block-separator\"\/>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Structure of the mitochondria<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<p class=\"wp-block-paragraph\">The mitochondria are composed of the following components:<\/p>\n\n\n\n<ol class=\"has-black-color has-text-color has-background wp-block-list\" style=\"background-color:#cafde9\"><li><strong>A<\/strong> <strong>double layer of a phospholipid membrane&nbsp;<\/strong>forming two compartments with<\/li><li><strong>an inner&nbsp;matrix<\/strong> and&nbsp;<\/li><li><strong>an intermembrane space<\/strong>, serving for the separation of the biochemical processes.<\/li><\/ol>\n\n\n\n<p class=\"wp-block-paragraph\"><br>Within the inner matrix, internal invaginations of the inner membrane form&nbsp;<\/p>\n\n\n\n<p class=\"has-background wp-block-paragraph\" style=\"background-color:#ccfdea\">4. <strong>cristae<\/strong>, which increase the surface area; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">within the inner membrane, you will find the<\/p>\n\n\n\n<p class=\"has-background wp-block-paragraph\" style=\"background-color:#c4f5e1\">5. <strong>terminal oxidation relating protein complexes<\/strong>&nbsp;(Fe-S-cluster proteins containing metals) and the&nbsp;<strong>ATP synthase<\/strong>&nbsp;(F<sub>0<\/sub>F<sub>1<\/sub>) (<strong>Figure 1<\/strong>).<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Functions and related metabolic processes<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<p class=\"wp-block-paragraph\">The primary role of the mitochondria is the&nbsp;<strong>production of ATP<\/strong>, the source of energy. But that\u2019s not the only thing that happens within there.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>DNA and protein synthesis<\/strong><\/li><li><strong>elongation and degradation of fatty acids<\/strong><\/li><li><strong>transportation of proteins<\/strong>&nbsp;and&nbsp;<\/li><li><strong>the fatty acid degradation<\/strong><\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><a href=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1.png\" target=\"_blank\" title=\"Mitochondria\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1-1024x540.png\" alt=\"\" class=\"wp-image-6307\" width=\"512\" height=\"270\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1-1024x540.png 1024w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1-300x158.png 300w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1-768x405.png 768w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1-1536x809.png 1536w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1-2048x1079.png 2048w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito-1.png 1600w\" sizes=\"auto, (max-width: 512px) 100vw, 512px\" \/><\/a><figcaption><strong>Figure 1. The features of the mitochondria<\/strong><\/figcaption><\/figure><\/div>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Production of ATP &#8211; terminal oxidation and electron transport<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\"><em>In the terminal oxidation\/electron transport chain,&nbsp;<strong>electron transmission is accompanied by a proton gradient<\/strong>&nbsp;between the two sides of the inner membrane. The formation of the proton gradient occurs through the complexes of the respiratory chain (ETC).<\/em><\/p>\n\n\n\n<ol class=\"wp-block-list\"><li><strong>Complex I.<\/strong> is responsible for the oxidation of the NADH, while electrons are released into the membrane and the protons are pumped into the intermembrane space.<\/li><li><strong>Complex II.<\/strong> is not a transmembrane protein, thus it can not pump out hydrogen. The produced hydrogen from the succinate-fumarate change should be transported to the next transmembrane proteins, complex III.<\/li><li><strong>Ubiquinone<\/strong> (UQ) is a kind of &#8220;postman&#8221; transporting the protons and electrons towards the next complex. When the UQ is fully equipped carries 2 protons and 2 electrons.<\/li><li><strong>Complex III.<\/strong> pumping out protons respectively, while electrons are travelling via membrane to the next complex.<\/li><li><strong>Complex IV.<\/strong> is responsible for the electron &#8220;sleigh ride&#8221; into the matrix.<\/li><li>Proton gradients are formed because the inner membrane is impermeable to protons. Protons return to the matrix through the proton channel, which is part of the <strong>ATP synthase<\/strong> (<strong>Complex V<\/strong>), a multi-subunit enzyme. The enzyme consists of F<sub>0<\/sub>F<sub>1<\/sub> subunits. F<sub>0<\/sub>\u00a0forms the proton channel, and F<sub>1<\/sub>\u00a0performs ATP synthesis (<strong>Figure 2<\/strong>).<\/li><\/ol>\n\n\n\n<p class=\"has-black-color has-text-color wp-block-paragraph\"><em>The difference in the concentration of the protons leads to a pH difference, i.e., the matrix is more alkaline than the membrane. Thus, the proton motive force is formed, so the free energy reduction is converted into electrochemical energy<\/em>.<\/p>\n\n\n\n<p class=\"has-black-color has-text-color wp-block-paragraph\"><em>The protons spontaneously return to the matrix according to the electrochemical gradient, which results in a reduction in free energy and is transformed by ADP phosphorylation into chemical energy in the form of ATP.<\/em><\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><a href=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1.png\" target=\"_blank\" title=\"Mitochondria\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1-1024x619.png\" alt=\"\" class=\"wp-image-6309\" width=\"512\" height=\"310\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1-1024x619.png 1024w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1-300x181.png 300w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1-768x464.png 768w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1-1536x928.png 1536w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1-2048x1237.png 2048w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito2-1.png 1600w\" sizes=\"auto, (max-width: 512px) 100vw, 512px\" \/><\/a><figcaption><strong>Figure 2. Proton gradient of the ETC, generation of ATP<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><em>The energy generated during the back oxidation of reduced coenzymes is used for the ATP synthesis from oxidative phosphorylation complexes from ADP and inorganic phosphate. <\/em><\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Inhibition of the complexes<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<p class=\"wp-block-paragraph\">Inhibiting the respiratory complexes lead to the lack of or less ATP production (Table 1). <\/p>\n\n\n\n<figure class=\"wp-block-table aligncenter is-style-stripes\"><table class=\"has-background\" style=\"background:linear-gradient(135deg,rgb(122,220,180) 0%,rgb(206,244,230) 100%)\"><thead><tr><th>Compound<\/th><th>Effects<\/th><\/tr><\/thead><tbody><tr><td><strong>Carbon dioxide (CO)<\/strong><\/td><td>Inhibiting cytochrome oxidase (<strong>Complex IV<\/strong>)<\/td><\/tr><tr><td><strong>Cyanide (CN<sup>&#8211;<\/sup>)<\/strong><\/td><td>Inhibiting cytochrome oxidase (<strong>Complex IV<\/strong>) <\/td><\/tr><tr><td><strong>Antimycin A<\/strong><\/td><td>Inhibits the electron transition from Cyt b and Cyt c1 (<strong>Complex III<\/strong>)<\/td><\/tr><tr><td><strong>Malonate <\/strong><\/td><td>Competitive inhibitor of Succinate dehydrogenase (<strong>Complex II<\/strong>)<\/td><\/tr><tr><td><strong>Rotenone<\/strong><\/td><td>Inhibits the electron transfer from the Fe-S centre to the UQ (<strong>Complex I<\/strong>)<\/td><\/tr><tr><td><strong>Oligomycin<\/strong><\/td><td>Specific inhibitors of the ATP synthase (<strong>Complex V<\/strong>)<\/td><\/tr><tr><td><strong>Dinitrophenol (DNP)<\/strong><\/td><td>Protonophore uncoupleing agent<\/td><\/tr><tr><td><strong>Thermogenin\/ Uncoupling protein 1 (UCP-1)<\/strong><\/td><td>Forms proton-conducting pore, no ATP is produced (a feature of brown adipocytes &#8211; heat production <a href=\"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/medical-lipid\/ucp1-thermogenin\/\">UCP1 \u2014 Thermogenin<\/a>)<\/td><\/tr><tr><td><strong>Atractyloside<\/strong><\/td><td>Inhibits adenine nucleotide exchange (ATP-ADP)<\/td><\/tr><\/tbody><\/table><figcaption><strong>Table 1. Effects of ETC inhibitors<\/strong><\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">There are several chemical agents capable to block\/alter different parts of the chain (Figure 3-4).<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><a href=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3.png\" target=\"_blank\" title=\"Mitochondria\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3-1024x686.png\" alt=\"\" class=\"wp-image-6319\" width=\"512\" height=\"343\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3-1024x686.png 1024w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3-300x201.png 300w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3-768x514.png 768w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3-1536x1029.png 1536w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3-2048x1371.png 2048w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito3.png 1600w\" sizes=\"auto, (max-width: 512px) 100vw, 512px\" \/><\/a><figcaption><strong>Figure 3. Categories of inhibitors<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large is-resized\"><a href=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4.png\" target=\"_blank\" title=\"Mitochondria\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4-1024x619.png\" alt=\"\" class=\"wp-image-6320\" width=\"512\" height=\"310\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4-1024x619.png 1024w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4-300x181.png 300w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4-768x464.png 768w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4-1536x928.png 1536w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4-2048x1237.png 2048w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/09\/Mito4.png 1600w\" sizes=\"auto, (max-width: 512px) 100vw, 512px\" \/><\/a><figcaption><strong>Figure 4. Inhibitors and their targets<\/strong><\/figcaption><\/figure><\/div>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Mitochondrial genome &#8211; mtDNA<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<p class=\"wp-block-paragraph\">The mitochondrial DNA consists of 16569 base-pairs of&nbsp;<strong>circular DNA&nbsp;<\/strong>of a<strong>&nbsp;bacterial origin<\/strong>, forming 37 genes that encode for:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>13 proteins<\/li><li>rRNAs<\/li><li>tRNAs<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Respiratory chain proteins encoded by the human mitochondrial genome:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li><strong>NADH dehydrogenase<\/strong> (Complex I)<\/li><li><strong>Succinate dehydrogenase<\/strong> (Complex II)<\/li><li><strong>Ubiquinone cytochrome C dehydrogenase<\/strong> (Complex III)<\/li><li><strong>Cytochrome oxidase<\/strong> (Complex IV)<\/li><li><strong>ATP synthase<\/strong> (Complex V)<\/li><\/ol>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Mutations in mtDNA<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<p class=\"wp-block-paragraph\">Mutations and injuries are more dangerous because <\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>the genome is <strong>close to the inner surface<\/strong> of the inner membrane<\/li><li><strong>reactive oxygen radicals <\/strong>can be produced in large quantities <\/li><li>there are&nbsp;<strong>no protective histone proteins; there is no DNA repair system<\/strong><\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Many of the mutations are generated by replication errors, which can not be corrected or repaired. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>During the ageing process, with time, such genetic errors became more common. Since the proteins of the respiratory chain (I, II, III, IV, V complexes) are encoded in the mitochondrial genome, and if mutated are injured, metabolic problems may occur. Some specific mutations may even cause crystals to appear within the mitochondria.<\/em><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Typical mutations are:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li><strong>LHON mutation<\/strong>&nbsp;(Leber\u2019s optical neuropathy)<\/li><li><strong>MERRF syndrome<\/strong>&nbsp;(Myoclonic epilepsy and ragged-red fibre disease)<\/li><\/ol>\n\n\n<\/span><span class=\"block-heading\" id=\"header_7\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">References<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<p class=\"wp-block-paragraph\"><span style=\"font-size: revert; color: initial;\">Snider MDS. Devlin\u2019s <strong>Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley &amp; Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Structure of the mitochondria<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Functions and related metabolic processes<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Production of ATP &#8211; terminal oxidation and electron transport<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Inhibition of the complexes<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Mitochondrial genome &#8211; mtDNA<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Mutations in mtDNA<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">References<\/h2><\/div>","protected":false},"excerpt":{"rendered":"<p>Structure of the mitochondria The mitochondria are composed of the following components: A double layer of a phospholipid membrane&nbsp;forming two compartments with an inner&nbsp;matrix and&nbsp; an intermembrane space, serving for the separation of the biochemical processes. Within the inner matrix, internal invaginations of the inner membrane form&nbsp; 4. cristae, which increase the surface area; within [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":1711,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1717","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Mitochondria &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/carbohydrate-metabolism\/mitochondria\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/pre-clinical\\\/biochemistry\\\/biochemistry-of-the-metabolism\\\/carbohydrate-metabolism\\\/mitochondria\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/pre-clinical\\\/biochemistry\\\/biochemistry-of-the-metabolism\\\/carbohydrate-metabolism\\\/mitochondria\\\/\",\"name\":\"Mitochondria &#8211; 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