Cell nucleus, mitochondrion, peroxysome Emese Pálfi Semmelweis University Department of Anatomy, Histology and Embryology - all organisms descended from a common ancestor cell - evolution by natural selection - cells are the smallest units of an organism - common features: cell membrane, DNA, cytoplasm - cell nucleus - cytoskeleton - RNA synthesis (transcription) and protein synthesis (translation) are separated The cell nucleus Nucelar envelope: Nuclear pores: - two concentric membane + - formed by nuclear pore complex perinuclear space - inner ring, annulus, outer ring - inner nuclear membrane is - selective active transport supported by the fetlike nuclear - nuclear localization signal (NLS) lamina (meshwork of interconnected - nuclear export signal (NES) proteins) - outer nuclear membrane is studded Nucleolus: with ribosomes - ribosomal RNA synthesis - directly connected to the - ribosome assembly endoplasmic reticulum (ER) Nucleoplasm - chromatin: DNA + histone proteins euchromatin: transcriptionally active less condensed heterochromatin: transcriptionally inactive highly condensed - non-histone proteins 5 µm - chromosomes are only visible during cell division - water, ions, RNA, soluble small molecules Barr-body: Inactive X-chromosome Chromosomes Somatic cells: two sets of 23 chromosomes 22 pairs of autosoms + 1 pair of sex chromosomes Mitochondrion established them as cell organelles Richard Altmann (1886) german pathologist mitos= "thread” chondrion= "granule" ”Powerhouse of the cell” Philip Siekevitz (1957) american biochemist Origin Endosymbiotic theory - prokaryotic cells - capable of implementing oxydative mechanisms Autogenous hypothesis - born by splitting off a portion of DNA from the nucleus of the eukaryotic cell - enclosed by membranes Structure Matrix Inner membrane Outer membrane Intermembrane space DNA, RNA, transcription, translation machinery → semiautonom Outer membrane: Porine: open, non-specific channel → <5kDa lets everything through → intermembrane space = cytosol (hins. <5kDa) Inner membrane: protein rich! (electron transport chain, proton pump, ATP synthase, special transporters) Contact points: TIM, TOM = protein translocators Intracellular location In most cells disordered, often along microtubules In some cells: where a lot of ATP is required Kidney tubule Heart muscle Spermatide Function Cellular respiration: Glycolysis endoxydation of food (sugar, fat) → pyruvate Krebs/ citric acid cycle → CO2 + high-energy electrons → Electron transport chain: H+ gradient → drives the ATP synthase More functions: - heat production (brown adipose tissue) - Ca2+ -storage - role in apoptosis - steps of steroid hormone synthesis Electron transport chain On both sides of the inner membrane creates an electrochemical gradient (= charge difference (membrane potential) + concentration gradient) Pass of two electrons → 10 protons are pumped out ATP synthase 4 H+ out → 1 ATP (3 H+) + transport system maintenance (1 H+) Toxins/membrane injury → energy transforms into warmth Brown adipose tissue → thermogenesis Mitochondreal diseases Kearns–Sayre syndrome (mitochondrial myopathy) pigmentary retinopathy cardiac conduction abnormalities weakness of facial, pharyngeal, trunk and extremity muscles Leigh syndrome (mtDNA mutation) failure to thrive progressive loss of mental and movement abilities „three parent baby” MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) Peroxysome - „microbody" - small (d= 0.1 - 1 μm) - outer lipid bilayer, inside finely granulated substance in some mammals (e.g., rat), the core crystallized in the middle (catalase, urate oxidase) Occurrence: all cells, but especially in those where detoxification (liver cells, renal tubules) or intensive lipid metabolism (myelin sheath, sebaceous gland) is running. Origin: either from ER or by division from an existing peroxysome Proteins are produced in the cytosol on free ribosomes and be with the help of peroxins (different proteins) are transported the cell organelle. Function Lipid synthesis and oxidation Detoxification (liver, kidney): phenol, ethanol, formaldehyde Protection against oxygen radicals Breakdown of fatty acid molecules Enzymes Peroxidase: withdraw hidrogen atoms from organic substrates using O2 RH2 + O2 H2O2 Catalase: 2 H2O2 2 H2O + O2 Other enzymes: Urine oxidase, fatty acid oxidases, D-amino acid oxidase Peroxisomal diseases Zellweger-Syndrom poor muscle tone (hypotonia) poor feeding seizures hearing loss vision loss distinctive facial features skeletal abnormalities Neonatal adrenoleukodystrophy hypotonia leukodystrophy vision and sensorineural hearing deficiencies Literature Alberts: Molecular biology of the cell (Third edition, 1994) Kovács: Sejttan (1999) Dr. Baksa: Miochondrium, peroxysom Dr. Kántor: Miochondrium, peroxysom Dr. Kántor: Zellkern, Zytoskeleton Dr. Zachar, Zsíros: Mitokondrium, peroxiszóma https://en.wikipedia.org/wiki/Prokaryote#/media/File:Celltypes.svg https://biologydictionary.net/cell-nucleus/ https://www.biologyexams4u.com/2012/06/nucleus-ultra-structure.html https://en.wikipedia.org/wiki/Kearns%E2%80%93Sayre_syndrome https://ghr.nlm.nih.gov/condition/leigh-syndrome#genes https://emedicine.medscape.com/article/946864-overview https://rarediseases.info.nih.gov https://bocaprepetc.weebly.com/atp-synthase.html .