Transcript PPS Lecture

Mitochondria ,Role &Function
GR.Zamani,
Pediatric Neurologist
Children’s Medical Center,Tums,Dec.2013
Mitochondria
• Organelles present in almost all human cells
• Produce bulk of energy for all cellular functions
• ATP production via the electron transport chain
• Over 1000 proteins localized to mitochondria
• 13 are mitochondrial-encoded
• Remainder are nuclear-encoded
Defect in mitochondrial function is the cause for
numerous inherited diseases
Problems Associated with Mitochondrial Cytopathies,
Brain
Developmental delays, mental retardation, dementia, seizures, neuro-psychiatric disturbances, atypical cerebral palsy,
migraines, strokes
Nerves
Weakness (which may be intermittent), neuropathic pain, absent reflexes
Gastrointestinal problem (gastroesophogeal reflux, delayed gastric emptying, constipation, pseudo-obstruction)
Muscles
Weakness, hypotonia, cramping, muscle pain
Kidneys
Proximal renal tubular wasting resulting in loss of protein, magnesium, phosphorous, calcium and other electrolytes
Heart
Cardiac conduction defects (heart blocks), cardiomyopathy
Liver
Hypoglycemia (low blood sugar), liver failure
Eyes
Visual loss and blindness
Ears
Hearing loss and deafness
Pancreas
Diabetes and exocrine pancreatic failure (inability to make digestive enzymes)
Systemic
Failure to gain weight, short stature, fatigue, respiratory problems including intermittent air hunger
Mitochondria Diseases
Mitochondria are responsible for producing
most of the energy that's needed for our cells
to function. In fact, they are motor house of
the cell providing energy .
A mitochondrial disease can shut down some
or all the mitochondria in the cells, cutting off
this essential energy supply.
Mitochondria
• Mitochondria are intracellular organelles found in almost all
human cells, responsible for aerobic metabolism through
oxidative phosphorylation, which leads to energy production as
(ATP).Each human cell contains on average hundreds to
thousands of mitochondria. The exception is mature RBCs,
which rely exclusively on anaerobic metabolism and contain no
mitochondria.
• Over 1000 proteins localized to mitochondria
• 13 are mitochondrial-encoded
• Remainder are nuclear-encoded
Causes of mitochondrial disease
• Mt.DNA (Nuclear DNA Mutation
• Mitochondria DNA inheritance
• Combination of mt.DNA and n.DNA defects
• Random occurrences
Mitochondria are under the dual control of
mitochondrial DNA and nuclear DNA.
Structure
• Mitochondria have a
double membrane
structure
• There is a single outer
membrane and a
folded inner
membrane
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Mitochondria are organized into 4
distinct compartments
•
•
•
Outer membrane:
Perforated with large
channels (porins) that allow
entry of molecules < 5000
kD
Enzymes involved in
mitochondrial lipid
synthesis
Outer membrane
• The outer mitochondrial membrane contains a
variety of enzymes involved in diverse activities
such as:
• elongation of fatty acids
• oxidation of epinephrine (adrenaline),
• and the degradation of tryptophan.
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Mitochondria are organized into 4
distinct compartments
•
•
•
Intermembrane space:
Enzymes that use newlymade ATP to phosphorylate
other nucleotides
Compartment into which H+
is pumped
Mitochondria are organized into 4
distinct compartments
•
•
•
•
•
Inner membrane:
Folded into christae to
maximize surface area
Proteins that carry out
redox reactions of the
electron transport chain
Proteins that synthesize
ATP
Transport proteins that
move molecules into and
out of the matrix
Inner membrane
• The inner membrane contains proteins with three
types of functions :
• those that carry out the oxidation reactions of the
respiratory chain composed of five enzyme
complexes(complex I,II,III,IV,V)
• ATP synthesis, which makes ATP in the matrix
• specific transport proteins that regulate the passage
of metabolites into and out of the matrix
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Mitochondria are organized into 4
distinct compartments
•
•
•
Matrix:
Internal space containing
enzymes for Krebs cycle
Contains mitochondrial
DNA, special ribosomes,
tRNAs, and enzymes
required for gene
expression
Function
• Mitochondria
are the site of most of the energy production in
eukaryotic cells . They use complex molecules and oxygen to
produce a high energy molecule know as ATP
(Adenosine
Triphosphate)
• process called aerobic respiration
• Energy production the mitochondria
has
been
called
the
"powerhouse of the cell".
• Mitochondria are very abundant in cells that require lots of energy.
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Mithochondrial function
• In addition to ATP generation through the respiratory
chain, mitochondria perform multiple other metabolic
functions, including pyruvate oxidation, the Krebs
cycle, fatty acid oxidation, and amino acid
metabolism. All of these tasks take place in the
matrix.
Other functios of Mithocondria
• Although the primary many metabolic function of mitochondria is to
convert organic materials into cellular energy in as ATP
mitochondria play other important roles such as:
• Apoptosis-Programmed cell death
• Glutamate-mediated excitotoxic neuronal injury
• Cellular proliferation , Regulation of the cellular redox state
• ,Heme synthesis and Steroid synthesis
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Although any abnormality in the oxidative pathways
could be technically designated as a mitochondrial
disorder, only defects in the respiratory chain are
traditionally referred to as primary mitochondrial
diseases
.
Thank You