Next Article in Journal
Micellar Hyaluronidase and Spiperone as a Potential Treatment for Pulmonary Fibrosis
Next Article in Special Issue
Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells?
Previous Article in Journal
Antitumor Effects of 5-Aminolevulinic Acid on Human Malignant Glioblastoma Cells
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 22
Issue 11
10.3390/ijms22115598
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study

by
Sara Laine-Menéndez
1,†,
Cristina Domínguez-González
1,2,3,†,
Alberto Blázquez
1,
Aitor Delmiro
1,
Inés García-Consuegra
1,
Miguel Fernández-de la Torre
1,
Aurelio Hernández-Laín
4,
Javier Sayas
5,
Miguel Ángel Martín
1,2 and
María Morán
1,2,*
1
Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’), 28041 Madrid, Spain
2
Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, 28029 Madrid, Spain
3
Deparment of Neurology, Neuromuscular Unit, Hospital 12 de Octubre, 28041 Madrid, Spain
4
Department of Pathology (Neuropathology), Hospital 12 de Octubre, 28041 Madrid, Spain
5
Department of Pneumology, Ventilation Unit, Hospital 12 de Octubre, 28041 Madrid, Spain
*
Author to whom correspondence should be addressed.
†
Equally contributed.
Int. J. Mol. Sci. 2021, 22(11), 5598; https://doi.org/10.3390/ijms22115598
Submission received: 6 April 2021 / Revised: 18 May 2021 / Accepted: 20 May 2021 / Published: 25 May 2021
(This article belongs to the Special Issue Molecular Mechanisms, Pathophysiology and Phenotypes of Mitochondrial Disorders)
Browse Figures
Review Reports Versions Notes

Abstract

Our goal was to analyze postmortem tissues of an adult patient with late-onset thymidine kinase 2 (TK2) deficiency who died of respiratory failure. Compared with control tissues, we found a low mtDNA content in the patient’s skeletal muscle, liver, kidney, small intestine, and particularly in the diaphragm, whereas heart and brain tissue showed normal mtDNA levels. mtDNA deletions were present in skeletal muscle and diaphragm. All tissues showed a low content of OXPHOS subunits, and this was especially evident in diaphragm, which also exhibited an abnormal protein profile, expression of non-muscular β-actin and loss of GAPDH and α-actin. MALDI-TOF/TOF mass spectrometry analysis demonstrated the loss of the enzyme fructose-bisphosphate aldolase, and enrichment for serum albumin in the patient’s diaphragm tissue. The TK2-deficient patient’s diaphragm showed a more profound loss of OXPHOS proteins, with lower levels of catalase, peroxiredoxin 6, cytosolic superoxide dismutase, p62 and the catalytic subunits of proteasome than diaphragms of ventilated controls. Strong overexpression of TK1 was observed in all tissues of the patient with diaphragm showing the highest levels. TK2 deficiency induces a more profound dysfunction of the diaphragm than of other tissues, which manifests as loss of OXPHOS and glycolytic proteins, sarcomeric components, antioxidants and overactivation of the TK1 salvage pathway that is not attributed to mechanical ventilation.
Keywords: mitochondrial diseases; diaphragm; thymidine kinase 2; respiratory failure mitochondrial diseases; diaphragm; thymidine kinase 2; respiratory failure

Share and Cite

MDPI and ACS Style

Laine-Menéndez, S.; Domínguez-González, C.; Blázquez, A.; Delmiro, A.; García-Consuegra, I.; Fernández-de la Torre, M.; Hernández-Laín, A.; Sayas, J.; Martín, M.Á.; Morán, M. Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study. Int. J. Mol. Sci. 2021, 22, 5598. https://doi.org/10.3390/ijms22115598

AMA Style

Laine-Menéndez S, Domínguez-González C, Blázquez A, Delmiro A, García-Consuegra I, Fernández-de la Torre M, Hernández-Laín A, Sayas J, Martín MÁ, Morán M. Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study. International Journal of Molecular Sciences. 2021; 22(11):5598. https://doi.org/10.3390/ijms22115598

Chicago/Turabian Style

Laine-Menéndez, Sara, Cristina Domínguez-González, Alberto Blázquez, Aitor Delmiro, Inés García-Consuegra, Miguel Fernández-de la Torre, Aurelio Hernández-Laín, Javier Sayas, Miguel Ángel Martín, and María Morán. 2021. "Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study" International Journal of Molecular Sciences 22, no. 11: 5598. https://doi.org/10.3390/ijms22115598

APA Style

Laine-Menéndez, S., Domínguez-González, C., Blázquez, A., Delmiro, A., García-Consuegra, I., Fernández-de la Torre, M., Hernández-Laín, A., Sayas, J., Martín, M. Á., & Morán, M. (2021). Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study. International Journal of Molecular Sciences, 22(11), 5598. https://doi.org/10.3390/ijms22115598

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop