diseases that result from abnormal mitochondrial function lu qiping 1070800106 april 15, 2011
TRANSCRIPT
Diseases that Result from Abnormal Mitochondrial
FunctionLu Qiping 1070800106
April 15, 2011
Mitochondrial Function
Essential organelle in eukaryotic cells Energy factory: oxidize fat, protein, carbohydrate generate ATP
run activities
a glucose36 ATPs
Mitochondria function much more than energy factory
Mitochondrial Function
Mitochondrial Function
It takes about 3000 genes to make a mitochondrion, mtDNA encodes just 37 of these genes, nuclear DNA encodes the remaining genes.
3% of the genes are allocated for making ATP, More than 95% are involved with other
functions.
Mitochondria are involved in • energy metabolism• calcium homeostasis 稳态
• lipid, cholesterol, heme 亚铁血红素 synthesis• Apoptosis 细胞凋亡
Mitochondrial Function
Given its fundamental role in the human body, defects of mitochondrial function can
have disastrous consequences.
Mitochondrial Disease
mtDNA and/or nuclear DNA mutation
Mitochondrial dysfunction
Mitochondrial-based diseases
Mitochondrial diseases are the result of either inherited 遗传的 or spontaneous 自发的 mutations in mtDNA or nDNA which lead to altered functions of the proteins or RNA molecules in mitochondria.
Mitochondrial Disease
Neurodegenerative disease神经退行性疾病
Neurodegenerative disease神经退行性疾病
Characterized by the progressive death of neurons.
Neurodegenerative Disease
Results in•memory loss •movement problems•Behavioral problems•Cognitive 认知 deficits •emotional alterations
Named after English doctor James Parkinson
Affects 1-2% of individuals over 60 years old
Motor syndrome
• Akinesia 失去活动能力
• Rigidity 僵硬
• Tremor 震颤
• imbalance
Parkinson’s Disease
PD is a degenerative disorder of the central nervous system. It results from the death of dopamine neurons 多巴胺神经元 in the substantia nigra （ SN）黑质 of midbrain.
Dopamine is a neurotransmitter 神经递质 that transmit impulses across the synapses 突触间隙 .
Parkinson’s Disease
Parkinson’s Disease
How do mitochondria involve in ?
In 1980s, young drug addicts reported with PD, due to a compound called MPTP in their heroin 海洛因 supply.
Parkinson’s Disease
MPTP is metabolized in the brain into MPP+.MPP+ selectively enters dopamine neurons, blocks oxidative phosphorylation 氧化磷酸化 by inhibiting mitochondrial complex I,results in increased oxidative stress, intracellular Ca2+ levels and excitotoxicity 兴奋毒性 , and decreased energy production.leading to the death of nerve cells in SN.
Then, the dopamine neurons from SN of PD patients were studied:
The complex I activity decreased remarkably and selectively.
Dopamine neurons are sensitive to mitochondrial dysfunction.
Parkinson’s Disease
What is the molecular mechanism ?
Risk Factors: toxin, genetic mutation, old age.
Brief Mechanism:
Parkinson’s Disease
PD genes
Mitophagy
Risk Factors: toxin, genetic mutation, old age.
Brief Mechanism:
Parkinson’s Disease
PD genes
Mitophagy
Is there a common pathway for the PD associated mutation
genes?
Perspective
The field of mitochondrial disease has progressed rapidly, but much remains to be
learnt about molecular mechanisms in pathogenesis and about how we might treat
patients with these disorders.
Some hypothesis were proposed, however, no clear mechanisms were
proved.
Thank you!
Parkinson’s Disease
MitophagyMitochondrial autophage. Protect cells from damaged mitochondria.Related proteins: PINK1 & PARKIN
Lysosome
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Parkinson’s Disease
Several PD associated mutant genes are identified
Parkinson’s Disease
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