| First Author | Russo S | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 19847 |
| PubMed ID | 36400945 | Mgi Jnum | J:365329 |
| Mgi Id | MGI:7387729 | Doi | 10.1038/s41598-022-24231-4 |
| Citation | Russo S, et al. (2022) Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. Sci Rep 12(1):19847 |
| abstractText | Barth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mitochondrial phospholipid cardiolipin (CL). Deregulation of CL biosynthesis and maturation in BTHS mitochondria result in a dramatically increased monolysocardiolipin (MLCL)/CL ratio associated with bioenergetic dysfunction. One of the most promising therapeutic approaches for BTHS includes the mitochondria-targeted tetrapeptide SS-31, which interacts with CL. Here, we used TAFAZZIN knockdown (Taz(KD)) mice to investigate for the first time whether in vivo administration of SS-31 could affect phospholipid profiles and mitochondrial dysfunction. The CL fingerprinting of Taz(KD) cardiac mitochondria obtained by MALDI-TOF/MS revealed the typical lipid changes associated with BTHS. Taz(KD) mitochondria showed lower respiratory rates in state 3 and 4 together with a decreased in maximal respiratory rates. Treatment of Taz(KD) mice with SS-31 improved mitochondrial respiratory capacity and promoted supercomplex organization, without affecting the MLCL/CL ratio. We hypothesize that SS-31 exerts its effect by influencing the function of the respiratory chain rather than affecting CL directly. In conclusion, our results indicate that SS-31 have beneficial effects on improving cardiac mitochondrial dysfunction in a BTHS animal model, suggesting the peptide as future pharmacologic agent for therapy. |
