Diseases that Result from
Abnormal Mitochondrial Function
Lu Qiping 1070800106
April 15, 2011
Mitochondrial Function
 Essential organelle in eukaryotic cells
 Energy factory: oxidize fat, protein, carbohydrate generate ATP run activities
a glucose36 ATPs
Mitochondrial Function
Mitochondria function much more
than energy factory
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
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.
mtDNA and/or nuclear DNA mutation
Mitochondrial dysfunction
Mitochondrial-based diseases
Mitochondrial Disease
Neurodegenerative disease
神经退行性疾病
Neurodegenerative Disease
 Characterized by the progressive death of neurons.
Results in
•memory loss
•movement problems
•Behavioral problems
•Cognitive认知 deficits
•emotional alterations
Parkinson’s Disease
 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
How do mitochondria involve in ?
Parkinson’s Disease
In 1980s, young drug addicts reported with
PD, due to a compound called MPTP in their
heroin海洛因 supply.
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.
Parkinson’s Disease
Dopamine neurons are sensitive to
mitochondrial dysfunction.
What is the molecular mechanism ?
Parkinson’s Disease
 Risk Factors: toxin, genetic mutation, old age.
 Brief Mechanism:
Mitophagy
PD genes
Parkinson’s Disease
 Risk Factors: toxin, genetic mutation, old age.
 Brief Mechanism:
Mitophagy
PD genes
Perspective
 Is there a common pathway
for the PD associated mutation genes?
 Some hypothesis were proposed, however,
no clear mechanisms were proved.
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.
Thank you!
Parkinson’s Disease
Mitophagy
Mitochondrial 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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