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Mejia et al. J Transl Genet Genom 2024;8:216-24 Journal of Translational
DOI: 10.20517/jtgg.2024.11
Genetics and Genomics

Original Article Open Access

Reduced protein kinase C delta in a high molecular
weight complex in mitochondria and elevated

creatine uptake into Barth syndrome B lymphoblasts

1
2
1
Edgard M. Mejia , Genevieve C. Sparagna , Donald W. Miller , Grant M. Hatch 1,3
1
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB R3E 0T6, Canada.
2
Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA.
3
Children’s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada.
Correspondence to: Dr. Grant M. Hatch, Department of Pharmacology and Therapeutics, Bannatyne Campus, University of
Manitoba, Max Rady College of Medicine, A205 Chown Bldg., 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. E-mail:
grant.hatch@umanitoba.ca
How to cite this article: Mejia EM, Sparagna GC, Miller DW, Hatch GM. Reduced protein kinase C delta in a high molecular
weight complex in mitochondria and elevated creatine uptake into Barth syndrome B lymphoblasts. J Transl Genet Genom
2024;8:216-24. https://dx.doi.org/10.20517/jtgg.2024.11

Received: 12 Mar 2024 First Decision: 6 May 2024 Revised: 6 May 2024 Accepted: 17 May 2024 Published: 30 May 2024

Academic Editor: Sanjay Gupta Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
Aim: Barth syndrome (BTHS) is a rare X-linked genetic disease in which mitochondrial oxidative phosphorylation is
impaired due to a mutation in the TAFAZZIN gene. The protein kinase C delta (PKCδ) signalosome exists as a high
molecular weight complex in mitochondria and controls mitochondrial oxidative phosphorylation.

Method: Here, we examined PKCδ levels in mitochondria of aged-matched control and BTHS patient B
lymphoblasts and its association with a higher molecular weight complex in mitochondria.

Result: Immunoblot analysis of blue-native polyacrylamide gel electrophoresis mitochondrial fractions revealed an
increase in total PKCδ protein expression in BTHS lymphoblasts compared to controls. In contrast, PKCδ associated
with a higher molecular weight complex was markedly reduced in BTHS patient B lymphoblasts compared to
controls. Given the decrease in PKCδ associated with a higher molecular weight complex in mitochondria, we
examined the uptake of creatine, a compound whose utilization is enhanced upon high energy demand. Creatine
uptake was markedly elevated in BTHS lymphoblasts compared to controls.

Conclusion: We hypothesize that reduced PKCδ within this higher molecular weight complex in mitochondria may

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
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