Physio Presentation.pptx

Mitochond r ion and Peroxiosom e

Mitochondria Description 0 0 0 0 0 0

-Powerhouses -Outer Membrane (porins) -Inner Membrane (ATPase, redox rxns-OP) -cristae -Intermembrane space

0 --Matrix (DNA, ribosomes,granules)

Functions o f the Mitochond rion

0 Energy production 0 Stores Calcium ions 0 Folds of cristae increases the surface area for the Electron

transport chain process

0 Mitochondrial matrix holds many enzymes 0 Programmed cell death. Occurs during injury or

mechanical damage 0 Build, breakdown and recycle products for proper cell functioning 0 Required for cholesterol and neurotransmitter metabolism

Mitochond rial Disorders

Kearns Sayre Syndrome 0 -onset in individuals younger than 20 years 0 -large-scale single deletions (or rearrangements)

of mitochondrial DNA (mtDNA), which are usually not inherited but occur spontaneously

0 -risk of maternal is 1 in 24 0 -ophthalmoparesis (muscles controlling the

eyelids and eye movement) and pigmentary retinopathy, cerebellar ataxia, cardiac conduction block, raised cerebrospinal fluid (CSF) protein content, and proximal myopathy.

0 -Affected children have short stature ,diabetes

mellitus, hypoparathyroidism, and Addison disease.

Leber’s Hereditary Optic Neuropathy - 3 mitochondrial DNA (mtDNA)

point mutations 11778 G to A, 3460 G to A and 14484 T to C -degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision -young adult males

Leigh’s Syndrome -mutations in mtDNA, although it is not always possible to identify the specific mutation cause mitochondria to fail or function improperly - Affects cells in brainstem and basal ganglia

which affect CNS and inhibit motor function - Movement disorders- rigidity, tremor and tics and seizures - Loss of appetite, vomiting, irritability, continuous crying and failure to thrive (in infants) - Episodes of lactic acidosis- general weakness,

kidney failure, and heart problems

Myoclonus Epilepsy with Ragged Red Fibers (MERRF) - mutation at position 8344 in the

mitochondrial genome disrupts for tRNA-Lys and synthesis of proteins essential for oxidative phosphorylation

- clumps of diseased mitochondria accumulate

in the subsarcolemmal region of the muscle fiber and appear as "Ragged Red Fibers" when stained with Goö moö ri trichrome stain

Ragged red fibers

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short stature hearing loss lactic acidosis exercise intolerance poor night vision

MELAS Syndrome MELAS is an abbreviation that stands for Mitochondrial Encephalopathy What causes MELAS? MELAS syndrome is caused by mutations in the genetic material (DNA) in the mitochondria. While most of our DNA is in the chromosomes in the cell nucleus, some of our DNA is in the mitochondrion.

What are the symptoms of MELAS? Due to the disturbed function of their cells' mitochondria, patients with MELAS develop brain dysfunction (encephalopathy) with seizures and headaches, as well as muscle disease with a buildup of lactic acid in the blood

Diabetes 0 Glucose and lipid metabolism are

largely dependent on mitochondria to generate energy in cells. 0 mtDNA (mitochondrial DNA)mutations strongly associate with diabetes 0 The nature of the diabetes can be type 1 or type 2 in nature depending on the severity of insulinopenia

Friedreich Ataxia 0 Caused by impaired iron metabolism in mitochondria 0 Loss of activities in iron-sulphur containing enzymes 0 Symptoms are caused by the wearing away of structures in areas

of the brain and spinal cord that control coordination and muscle movement

Peroxisom es What are Pe roxisomes?

Peroxisomes 0 Spherical organelles with single membrane and

diameter approximately 0.15 – 0.5 micro m 0 Their enzymes are produced by free polysomes 0 Peroxisomes are found in all eukaryotic cells. They contain oxidative enzymes, such as catalase and urate oxidase, at such high concentrations that in some cells the peroxisomes stand out in electron micrographs because of the presence of a crystalloid core

Cont’d Like mitochondria, peroxisomes are major sites of oxygen utilization. One hypothesis is that peroxisomes are a vestige of an ancient organelle that performed all the oxygen metabolism in the primitive ancestors of eukaryotic cells. When the oxygen produced by photosynthetic bacteria first began to accumulate in the atmosphere, it would have been highly toxic to most cells. Peroxisomes might have served to lower the intracellular concentration of oxygen, while also exploiting its chemical reactivity to perform useful oxidative reactions. According to this view, the later development of mitochondria rendered peroxisomes largely obsolete because many of the same reactions—which had formerly been carried out in peroxisomes without producing energy—were now coupled to ATP formation by means of oxidative phosphorylation. The oxidative reactions performed by peroxisomes in present-day cells would therefore be those that have important functions not taken over by mitochondria.

Functions • • • • •

Beta oxidation of very long chain fatty acids Synthesis and degradation of Hydrogen peroxide Cholesterol synthesis Bile acid synthesis Synthesis of specialized phospholipids required for nerve cells myelination

Peroxisom al Disorders

Zellweger syndrome 0 usually fatal within the first year of life

Neonatal Adrenoleukodystrophy 0 usually fatal within the first 10 years

Infantile Refsum Disease 0 children with this disorder with time and patience can

develop some degree of motor, cognitive, and communication skills 0 Death occurs in the 20’s

Rhizomelic Chondrodysplasia Punctata 0 in its most severe form is fatal within the first year or

two of life 0 survival into the teens has been known to occur 0 characterized by shortening of the proximal limbs

X-linked adrenoleukodystrophy (X-ALD) 0 Affecting about one in 20,000 males 0 Deficiency in the enzyme that breaks down VLCFAs,

which then accumulate in the myelin and adrenal glands 0 Onset of X-ALD-related neurological symptoms occurs at about five-12 years of age, with death occurring within one to 10 years after onset of symptoms

X-ALD 0 Common symptoms of X-ALD also include behavioral

changes such as abnormal withdrawal or aggression, poor memory, dementia, and poor academic performance 0 Other symptoms are muscle weakness and difficulties with hearing, speech, and vision 0 As the disease progresses, muscle tone deteriorates, swallowing becomes difficult and the patient becomes comatose 0 Unless treated with a diet that includes Lorenzo's oil, the disease will result in paralysis, hearing loss, blindness, vegetative state, and death

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