Mitochondrial impairment and synaptic dysfunction are associated with neurological defects in iPSCs-derived cortical neurons of MERRF patients

Table 2 The effects of m.8344A > G mutation on the biological function of neural cells derived from MERRF-iPSCs

	M1 MERRF patient			M3 MERRF patient
	M1^High			M3^Med
	iPSC	iNSC	Neuron	iPSC	iNSC	Neuron
m.8344A > G mutation level (%)	41.1 ± 1.4	38.7 ± 1.4	42.5 ± 1.7	28.8 ± 1.1	27.6 ± 1.9	34.0 ± 2.9
OXPHOS^a
COXII	↓	↓		↑	ND
SDHB	ND	↓		↑	ND
ATP5A	ND	ND		ND	ND
Respiration rate^a
Basal	↓	↓		ND	ND
ATP-coupled	↓	↓		ND	↓
Maximal	↓	↓		ND	↓
Proton leak	ND	ND		ND	ND
ROS levels^a	ND	↑	↑	ND	↑	↑
Antioxidant enzymes^a
Catalase	↑	↑		↑	↑
MnSOD	ND	↓		ND	ND
GPx4	↑	ND		↑	ND
Characteristic markers^a
Stemness markers	ND			ND
NSC specific markers		ND			ND
Pan neuron markers			ND			ND
Neuron cell death^a			↑			↑
Synaptic vesicular proteins^b
Synaptophysin			↓			↓
vGLUT2			↓			↓
Excitatory receptors^b
AMPARs			↓			↓
NMDAR1			ND			↓
Neuronal function
Spontaneous MFR^a			↓			↓
Neuron network^b			↓			↓
Evoked response^b			↓			↓

a: compared with isogenic control cells of subline; b: compared with M3^Low neuron
AMPARs α amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, ATP5A ATP synthase α subunit, SDHB succinate dehydrogenase complex iron sulfur subunit b, COXII cytochrome c oxidase subunit II, GPx4 glutathione peroxidase 4, iNSC induced neural stem cells differentiated from iPSCs, MFR mean firing rate, MnSOD manganese-dependent superoxide dismutase, ND no difference, NMDAR1 N-methyl-d-aspartate receptor 1, vGLUT2 vesicular glutamate transporter 2. ↓, decreased; ↑, increased

ISSN: 1423-0127