Table 2 Neurodegenerative disease: mitochondrial dysfunction in patients’ derived stem cell models
Neurodegenerative disease | Cells type | Oxidative stress | Mitochondrial dynamics | Oxphos metabolism | Organelle interplay | References |
|---|---|---|---|---|---|---|
Alzheimer disease | ||||||
 Sporadic | iPSC | Increased oxidative stress | – | – | – | Hossini et al. 2015 |
 Sporadic | Cortical neurons | – | Impaired mitophagy, increased mitochondrial fragmentation | Reduced ATP level | – | Fang et al. [176] |
 Sporadic | Cortical neurons | Increased ROS and oxidative stress with mtDNA damage | Normal level of dynamics proteins | Increased protein expression of NDUFB8, UQCRC2, MTCO1, ATP5A | – | Birnbaum et al. 2018 |
 PSEN1 | Cortical neurons | – | Aberrant mitochondrial network size, morphology, and trafficking Dynamics proteins deregulation | Lower expression levels of cytochrome c oxidase (complex IV), cytochrome c reductase (complex III), succinate dehydrogenase (complex II), NADH: CoQ reductase (complex I), and ATP synthase (complex V) | Impaired lysosomal function with consequent accumulation of damaged mitochondria | Martin-Maestro et al. [174]; Martin-Maestro et al. 2017; Li et al. 2020 |
 PSEN1 | Cholinergic neurons | Increased ROS and oxidative stress with mtDNA damage | – | Reduced ATP level | – | Oka et al. 2016 |
 PSEN1 | Astrocytes | Increased ROS | – | – | – | Oksanen et al. 2017 |
 APP | Cortical Neuron | – | Impaired mitophagy, increased mitochondrial fragmentation | Reduced ATP level | – | Fang et al. [176] |
Amyotrophic lateral sclerosis | ||||||
 C9orf72 | Motor neurons | Increased ROS and oxidative stress with mtDNA damage | Aberrant mitochondrial morphology | Reduced basal and maximal respiration | ER stress | Lopez-Gonzalez, 2016; Mehta et al. 2021; Dafinca et al. 2016 |
 FUS | Motor neurons | – | Aberrant mitochondrial trafficking | ER-mitochondrial overlay | – | Guo et al. 2018 |
 TARDBP | Motor neurons | – | Reduced mitochondrial motility | – | – | Fazal et al. 2021 |
 SOD1 | Motor neurons | Increased oxidative stress | Aberrant mitochondrial morphology and trafficking | Reduced ATP level | ER stress | Günther et al. 2022; Kiskinis et al. 2014 |
Huntington disease | ||||||
 HD | Cortical neurons | – | – | Reduce maximal respiratory capacity | – | An et al. 2012 |
Parkinson disease | ||||||
 LRRK2 | iPSC | Increased oxidative stress | – | – | – | Nguyen et al. 2011 |
 LRRK2 | Dopaminergic neurons | Increased oxidative stress and mtDNA damage | Reduced mitochondrial content and trafficking. Drp1-mediated dysfunction with mitochondrial fragmentation | Reduced maximal respiratory capacity and ATP/ADP level. Undetectable protein expression of NDUFB8 and COX II, decreased levels of UQCRC2 | – | Schwab et al. 2017; Nguyen et al. 2011; Sanders et al. 2014; Su et al. 2013 |
 PARK2 | Neurons | Increased oxidative stress | Abnormal mitochondrial morphology | – | Aberrant tubulovesicular organelle adjacent to Golgi | Imaizumi et al,, [185] |
 PARK2 | Neuropeptidergic Neurons | – | – | – | Increased ER-Mitochondria contact sites | Valadas et al. 2018 |
 PARK2 | Dopaminergic Neurons | Increased ROS | Abnormal mitochondrial content and morphology | Reduced Complex I | Increased ER-Mitochondria contact sites | McLelland et al. 2017; Chung et al. 2016; Zanon et al. 2017; Shaltouki et al. 2015 |
 PINK1 | iPSC | Increased oxidative stress | – | – | – | Nguyen et al. 2011; Cooper et al. 2012 |
 PINK1 | Neuropeptidergic Neurons | – | – | – | Increased ER-Mitochondria contact sites | Valadas et al. 2018 |
 PINK1 | Dopaminergic neurons | Increased ROS | Abnormal mitochondrial morphology | Reduced level of ATP | – | Chung et al. 2016; Vos et al. 2017 |
 SNCA | Dopaminergic neurons | Increased oxidative stress | Abnormal mitochondrial morphology and trafficking. Reduction of DRP1expression | Reduced maximal respiratory capacity and ATP production | ER stress; reduced ER-mitochondria contact sites | Zambon et al. 2019; Little et al. 2018; Paillusson et al. 2017; Prots et al. 2018 |
 GBA | Dopaminergic neurons | Increased oxidative stress | Abnormal mitochondrial morphology. Reduction of DRP1, OPA1 and MFN1 expression | Reduced maximal respiratory capacity and ATP production. Reduced Complex I activity | ER stress Reduction of mitochondrial-lysosomal co-localization | Schöndorf et al. 2018 |