|
| Pathology | Proteins involved
(expression level and/or mutation) | Mitochondrial phenotype | Mechanisms of pathophysiology involving mitochondria |
|
| Alzheimer disease | MFN1, MFN2, OPA1 ↓↓
DRP1, FIS1 ↑↑
KINESIN mutation | Fragmentation, disruption of cristae structure, reduction in number of mitochondria in dendrites, impaired mitochondrial trafficking, defects in KGDH complex, PDH complex and COX. | β amiloyd accumulation and interaction with DRP1, enhanced CDK1 activity, altered interaction between mitochondria and Kinesin motor complex in cerebral cortex [77–79]. |
|
| Huntington’s disease | MFN1, MFN2, OPA1 ↓↓
DRP1, FIS1 ↑↑
HTT mutation | Fragmentation; impaired mitochondrial trafficking, defects in SDH (complex II) and Aconitase. | HTT interaction with DRP1, increased calcineurin and DRP1 activity, redistribution of kinesin and dynein motor complexes in striatal neurons [80–82]. |
|
| Parkinson disease | Parkin mutation or ↓↓
Pink1 mutation or ↓↓
DJ-1 mutation
DRP1 ↓↓
MFN2
α-synuclein mutation
LRRK2 mutation | Fragmentation, impaired mitochondrial trafficking. | Altered interaction between mitochondria and motor complexes, impaired mitophagy of damaged mitochondria in substantia nigra [74, 75, 83–86]. |
|
| Amiotrophic lateral sclerosis | SOD mutation
GEFmutation
TDP-43 mutation | Fragmentation, disruption of cristae structure with expansion of IMS, impaired mitochondrial trafficking, complex I dysfunctions. | Toxicity associated to the formation of aggregates of mutant SOD, in subsarcolemmal region of muscles and anterior horn neurons of lumbar spinal cord [87–93]. |
|
| Autosomal dominant optic atrophy | OPA1 mutation | Fragmentation, complex I dysfunctions. | Major sensitivity to death stimuli in retinal ganglion cells and optic nerve [94–98]. |
|
| Charcot Marie Tooth Type 2 | MFN1 mutation
GDAP1mutation | Fragmentation (MFN1 mut) or elongation (GDAP1 mut). | MFN1: probably alteration in ER-mitocondria tethering and Calcium signalling [99]; GDAP1: altered localization of GDAP1 [100]. |
|
