Blood cell respiration rates and mtDNA copy number: A promising tool for the diagnosis of mitochondrial disease

Alonso, Martina; Zabala, Cristina Zoco; Mansilla, Santiago; Brun, Laureana De; Martínez, Jennyfer; Garau, Mariela; Rivas, Gabriela; Acosta, Cecilia; Lens, Daniela; Cerisola, Alfredo; Graña, Martín; Naya, Hugo; Puentes, Rodrigo; Spangenberg, Lucía; Raggio, Víctor; Lemes, Aída; Castro, Laura; Quijano, Celia

doi:10.1016/j.mito.2021.09.004

Cited by 5 publications

(18 citation statements)

References 90 publications

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“…In PBMCs, most of the respiratory parameters remained unchanged, but a significant increase in non-mitochondrial oxygen consumption rate was observed in the patient cells with respect to the controls (Additional file 3 : Fig. S3), in agreement with our previous report [ 7 ]. Non-mitochondrial respiration is usually linked to an increase in the activity of oxygen-consuming enzymes (such as NAD(P)H oxidases) or other processes that can produce oxidant species [ 17 ].…”

Section: Resultssupporting

confidence: 91%

“…Since respiratory rates of PBMCs decay with age [ 33 ] and are reported to be higher in females than males [ 34 ], we compared the oxygen consumption rate of the patient with those of three healthy control male patients (5, 7 and 10 years old) from a recent study published by our group [ 33 ]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…B Respiratory parameters for the patient were determined from the graph described above. Control values were obtained from male pediatric subjects with 5, 7 and 10 years, the mean values of these subjects were published previously [ 33 ]. C Respiratory parameters were normalized considering the number of mtDNA copies of the patient (299 mtDNA copies/cell), and control subjects (416, 322 and 200 mtDNA copies/cell, for the 5, 7 and 10 years old male controls, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…Platelet and PBMCs isolation and oxygen consumption rate (OCR) analyses were performed as previously described [ 7 ]. Briefly, blood samples were obtained in BD Vacutainer tubes containing EDTA after an overnight fast.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsies [ 7 ]. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using NGS.…”

Section: Introductionmentioning

confidence: 99%

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Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy

et al. 2023

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The SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients' mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy

et al. 2023

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Clinical drug interactions between linezolid and other antibiotics: For adverse drug event monitoring

Shu,

Huo,

Yin

et al. 2024

Pharmacology Res & Perspec

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Detailed data on safety associated with drug–drug interactions (DDIs) between Linezolid (LZD) and other antibiotics are limited. The aim of this study was to investigate the safety signals related to these DDIs and to provide a reference for clinically related adverse drug event monitoring. Adverse event (AE) information from 1 January 2004 to 16 June 2022 of the target antibiotics including LZD using alone or in combination with LZD was extracted from the OpenVigil FDA data platform for safety signal analysis. The combined risk ratio model, reporting ratio method, Ω shrinkage measure model, and chi‐square statistics model were used to analyze the safety signals related to DDIs. Meanwhile, we evaluated the correlation and the influence of sex and age between the drug(s) and the target AE detected. There were 18991 AEs related to LZD. There were 2293, 1726, 4449, 821, 2431, 1053, and 463 AE reports when LZD was combined with amikacin, voriconazole, meropenem, clarithromycin, levofloxacin, piperacillin‐tazobactam, and azithromycin, respectively. Except for azithromycin, there were positive safety signals related to DDIs between LZD and these antibiotics. These DDIs might influence the incidence of 13, 16, 7, 7, 6, and 15 types of AEs, respectively, and is associated with higher reporting rates of AEs compared with use alone. Moreover, sex and age might influence the occurrence of AEs. We found that the combinations of LZD and other antibiotics are related to multiple AEs, such as hepatotoxicity, drug resistance and electrocardiogram QT prolonged, but further research is still required to investigate their underlying mechanisms. This study can provide a new reference for the safety monitoring of LZD combined with other antibiotics in clinical practice.

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Phenotypic expression of the m.3243A > G variant not only depends on heteroplasmy or haplotype

Finsterer¹,

Mehri²

2023

Clinical Biochemistry

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Blood cell respiration rates and mtDNA copy number: A promising tool for the diagnosis of mitochondrial disease

Cited by 5 publications

References 90 publications

Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy

Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy

Clinical drug interactions between linezolid and other antibiotics: For adverse drug event monitoring

Phenotypic expression of the m.3243A > G variant not only depends on heteroplasmy or haplotype

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