Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts

Janny Piñeiro-Llanes; Silveli Suzuki-Hatano; Ananya Jain; Sree Venigalla; Manasi Kamat; Kari B Basso; William T Cade; Chelsey S Simmons; Christina A Pacak

doi:10.1016/j.biomaterials.2024.122922

Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts

Biomaterials. 2025 Apr:315:122922. doi: 10.1016/j.biomaterials.2024.122922. Epub 2024 Oct 26.

Authors

Janny Piñeiro-Llanes¹, Silveli Suzuki-Hatano², Ananya Jain³, Sree Venigalla⁴, Manasi Kamat⁵, Kari B Basso⁶, William T Cade⁷, Chelsey S Simmons⁸, Christina A Pacak⁹

Affiliations

¹ J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA. Electronic address: jpineiro@ufl.edu.
² Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, 32610, USA. Electronic address: silvelisuzuki@gmail.com.
³ J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA. Electronic address: ananyajain@ufl.edu.
⁴ Department of Neurology and Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, 55455, USA. Electronic address: venig004@umn.edu.
⁵ Department of Chemistry, University of Florida, Gainesville, FL 32611, USA. Electronic address: manasi@ufl.edu.
⁶ Department of Chemistry, University of Florida, Gainesville, FL 32611, USA. Electronic address: kari.basso@chem.ufl.edu.
⁷ Doctor of Physical Therapy Division, Duke University, Durham, NC, 27710, USA. Electronic address: todd.cade@duke.edu.
⁸ J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA; Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA. Electronic address: css@ufl.edu.
⁹ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, 32610, USA; Department of Neurology and Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, 55455, USA. Electronic address: cpacak@umn.edu.

PMID: 39509858
PMCID: PMC11625619 (available on 2026-04-01)
DOI: 10.1016/j.biomaterials.2024.122922

Abstract

Fibroblast-ECM (dys)regulation is associated with a plethora of diseases. The ECM acts as a reservoir of inflammatory factors and cytokines that mediate molecular mechanisms within cardiac cell populations. The role of ECM-mitochondria crosstalk in the development and progression of cardiac disorders remains uncertain. We evaluated the influence of ECM produced by stromal cells from patients with the mitochondrial cardiomyopathy (Barth syndrome, BTHS) and unaffected healthy controls on cardiac fibroblast (CF) metabolic function. To do this, cell-derived matrices CDMs were generated from BTHS and healthy human pluripotent stem cell-derived CFs (hPSC-CF) and used as cell culture substrates. BTHS CDMs negatively impacted the mitochondrial function of healthy hPSC-CFs while healthy CDMs improved mitochondrial function in BTHS hPSC-CFs. Mass spectrometry comparisons identified 5 matrisome proteins differentially expressed in BTHS compared to healthy CDM. Our results highlight a key role for the ECM in disease through its impact on mitochondrial function.

Keywords: Barth syndrome; Cardiac fibroblasts; Cell derived matrices; Extracellular matrix; Mitochondria.

MeSH terms

Barth Syndrome* / metabolism
Barth Syndrome* / pathology
Cells, Cultured
Extracellular Matrix* / metabolism
Female
Fibroblasts* / metabolism
Humans
Male
Mitochondria / metabolism
Myocardium / metabolism
Myocardium / pathology

Abstract

MeSH terms

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