Table 1.
Oxidative phosphorylation in spinal muscular atrophy
| SMA type/model | Respiration rate | Cellular ATP levels | Enzyme activity | Enzyme | Transcript expression | Transcripts | Protein expression | Proteins | References |
|---|---|---|---|---|---|---|---|---|---|
| Patient skeletal muscle fibres: vastus lateralis of quadriceps (SMA type unknown; mean age 5.8 years) | Reduced | Reduced | Complex I; II–III; IV; PDHC; citrate synthase | [20] | |||||
| Patient skeletal muscle (Types 1–3) | Reduced | Complex II; IV; citrate synthase | Reduced | MT-CO1; COX4 | [21] | ||||
| Patient muscle (muscle group and SMA type unknown; mean age 3.1 years) | Reduced | Complex I; II; III; I–III; II–III; IV; V; citrate synthase | [22] | ||||||
| Patient quadriceps femoralis muscle (Types 1 and 3) | Reduced (Type 1) | NDUFB1; CYC1; SLC25A4 | [23] | ||||||
| Patient quadriceps/paraspinal muscle (Types 1–3) | Reduced | Complex I; II; II–III; IV; citrate synthase | Reduced | MT-ND1; SDHA; MT-CO1; MT-CO2; COX4I1; MT-ATP6 | Reduced | SDHA; MT-CO1; MT-CO2; COX4I1 | [24] | ||
| Patient-derived iPSC-MNs/astrocytes | No change (astrocytes) | No change | Complex II, IV | [27] | |||||
| Type 1 patient-derived myoblasts/myotubes | Reduced (myoblasts) | No change (at baseline) | [29] | ||||||
| Spinal cord from Taiwanese mice (P5, P8)a | Reduced | [28] | |||||||
| Heart from Taiwanese mice (P1)a | Increased | MT-ATP6 | [30] | ||||||
|
Spinal MNs from Hung–Li SMA mice (P9)b Cultured MNs from SMN∆7 mice (E12.5)b |
Reduced | Reduced | [26] | ||||||
| Flexor tibialis and extensor plantaris (fast-twitch) and extensor soleus (slow-twitch) muscles from Smn∆7/∆7; huSMN2+/+micec |
Reduced (fast-twitch) No change |
Complex I; II; IV; citrate synthase |
No change | NDUFB8; SDHB; UQCRC2; MT-CO1; ATP5A | [31] | ||||
| Smn morphant zebrafish embryos | Reduced | Reduced | ATP5A | [28] |
All five complexes of the oxidative phosphorylation system show alterations in enzyme activity. Expression changes are found in transcripts and proteins encoded by both the nuclear and mitochondrial (denoted by ‘MT-’) genomes across all five complexes: MT-ND1, NDUFB1, and NDUFB8 (complex I); SDHA and SDHB (complex II); CYC1 and UQCRC2 (complex III); MT-CO1, MT-CO2, COX4, and COX4I1 (complex IV); ATP-5A, and MT-ATP6, and SLC25A4 (complex V). Mouse models of SMA are defined as severea, intermediateb, or mildc (reflecting SMA Types 1, 2, and 3/4, respectively). iPSC induced pluripotent stem cell, MNs motor neurons, PDHC pyruvate dehydrogenase complex, SMA spinal muscular atrophy, SMN survival motor neuron