Mitochondria Flashcards
(50 cards)
Mitochondrial dysfunction in neurodegenerative disorders
- maybe due to direct effects in mitochondrial proteins/quality control failures
- sometimes secondary to oxidative stress, protein aggregation
- always leads to increased oxidative stress and decreased energy (inefficient ATP production)
Role of mit
- Production of NADH and energy (ATP)
- Production of metabolites
- Ca2+ storage organelles
- Production of ROS
- Initiator of the apoptotic cascade
Positive roles of mit
- Production of NADH and energy (ATP)
- Production of metabolites necessary for cell function
- Ca2+ storage organelles (esp in neurons to prevent calcium build-up)
BAD effects of mit
- Production of ROS
5. Initiator of the apoptotic cascade
Mitochondria balance between ___ & _____
fission and fusion
Proteins involved in mitochondrial fusion:
- Mitofusin (Mfn) 1 and 2
- Optic atrophy (OPA) 1
Proteins involved in mitochondrial fission:
- Fis 1
- Dynamin-related protein (Drp) 1
- Endophilin B1
Fusion
stimulated by energy demand and stress
Fission
generates new organelles and facilitates quality control
allows mit trafficking w/in the cell
Normal mit look like ____
in absence of fission they look like ____
in absence of fusion looks like ____
WORMS
no fission = dense reticulum –concentrated/mit can’t localize properly (won’t get mit to periphery of cell)
no fusion = dots–looks very fragmented
At any time in the cells there is a mix of ____ & ____ mitochondria, due to the balance between ____ & ______
elongated & short;
fusion & fission
Mitochondrial dynamics
- Fragmentation facilitates recruitment of mitochondria to cellular compartments in need of ATP (axon terminals, dendrites)
- Mitochondrial fusion may represent a way to cope with “stress” and mtDNA mutations
- Increased fusion of mitochondria inhibit/retard apoptosis
- Apoptosis is normally associated with mitochondria fission
role of mit fragmentation
Fragmentation facilitates recruitment of mitochondria to cellular compartments in need of ATP (axon terminals, dendrites)
Apoptosis is normally associated with ____ (fusion vs. fission)
FISSION
increased fusionPREVENTS apoptosis
Mitochondrial defects mainly affect tissues with…
Mitochondrial defects mainly affect tissues with high energy demand
(nervous system, skeletal muscle)
Pathologies associated with mtDNA
mutations
Mitochondrial encephalomyopathies
mix of neurological and myopathic symptoms: myoclonic seizures, ataxia, muscle weakness
Pathologies associated Mitochondria
damage/dysfunction
PD, AD, HD, ALS
Pathologies associated Aberrant mitochondria dynamics (transport,
fusion/fission)
- Charcot-Marie-Tooth type 2A (CMT2A)–classical axon-sensory motor neuropathy
- Dominant Optic Atrophy (bilateral degeneration of optic nerve), other peripheral neuropathy
- And PD, AD, HD, ALS
Mit fusion allows
coping with stress
fusion leads to mixing of Mit DNA will compensate for deficits
Mit dysfunction in AD
-The activity of the mitochondrial respiratory chain is impaired in AD
brains and fibroblasts from patients.
-Oxidative damage is an early event in AD and increases production of
A-beta
Mit dysfunction in PD
-Toxins that inhibit complex I induce Parkinson, and complex I
dysfunction is observed in PD patients and animal models.
- Reduction of coenzyme Q (essential cofactor for mit function) levels in PD brain and peripheral cells
- Many proteins implicated in the development of PD (parkin, PINK1, DJ-1,
etc.) are involved in mitophagy and affect mitochondrial functions.
In PD and AD neurons, mitochondrial DNA accumulates more mutations
than in normal cells. WHY?
mit dysfunction –> ox stress –> further damage and dysfunction
_______ has also been proposed as a potential mechanism
underlying mitochondrial dysfunctions in neurodegenerative diseases such
as AD, HD and PD.
Altered mitophagy
Leads to the accumulation of dysfunctional mitochondria in neurons
Mit dysfunction in HD
- Impaired ability to store Ca++ . Mitochondria depolarization occurs at lower Ca++ concentration than normal
- Leakage of cytochrome c
- Increased mitochondrial fission
- Impaired mitochondrial import
- Decreased activity of mitochondrial Complexes II and III and decreased production of ATP
