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Study · In vitro (cells) · 2021

2 results

Diverse mitochondrial abnormalities in a new cellular model of TAFFAZZIN deficiency are remediated by cardiolipin-interacting small molecules.

Anzmann AF, Sniezek OL, Pado A, Busa V, Vaz FM, Kreimer SD, DeVine LR, Cole RN, Le A, Kirsch BJ, Claypool SM, Vernon HJ

The Journal of biological chemistry24 Jul 2021Cited by 23 (Europe PMC)

PMID34314685 (opens in a new tab)PMCIDPMC8384898 (opens in a new tab)DOI10.1016/j.jbc.2021.101005 (opens in a new tab)PepBankPUB-34314685
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Summary

Barth syndrome (BTHS) is an X-linked disorder of mitochondrial phospholipid metabolism caused by pathogenic variants in TAFFAZIN, which results in abnormal cardiolipin (CL) content in the inner mitochondrial membrane. To identify unappreciated pathways of mitochondrial dysfunction in BTHS, we utilized an unbiased proteomics strategy and identified that complex I (CI) of the mitochondrial respiratory chain and the mitochondrial quality control protease presenilin-associated rhomboid-like protein (PARL) are altered in a new HEK293-based tafazzin-deficiency model. Follow-up studies confirmed decreased steady state levels of specific CI subunits and an assembly factor in the absence of tafazzin; this decrease is in part based on decreased transcription and results in reduced CI assembly and function. PARL, a rhomboid protease associated with the inner mitochondrial membrane with a role in the mitochondrial response to stress, such as mitochondrial membrane depolarization, is increased in tafazzin-deficient cells. The increased abundance of PARL correlates with augmented processing of a downstream target, phosphoglycerate mutase 5, at baseline and in response to mitochondrial depolarization. To clarify the relationship between abnormal CL content, CI levels, and increased PARL expression that occurs when tafazzin is missing, we used blue-native PAGE and gene expression analysis to determine that these defects are remediated by SS-31 and bromoenol lactone, pharmacologic agents that bind CL or inhibit CL deacylation, respectively. These findings have the potential to enhance our understanding of the cardiac pathology of BTHS, where defective mitochondrial quality control and CI dysfunction have well-recognized roles in the pathology of diverse forms of cardiac dysfunction.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In tafazzin-deficient HEK293 cells, SS‑31 remediated the reduced complex I levels.

    In plain wordsIn cells lacking tafazzin, SS‑31 corrected the low levels of a mitochondrial protein complex.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseComplex I levels in tafazzin-deficient cells
    Study

    humann: not reported in source

    HEK293-based tafazzin-deficient cells
    Outcome group
    Mitochondrial function · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    To clarify the relationship between abnormal CL content, CI levels, and increased PARL expression that occurs when tafazzin is missing, we used blue-native PAGE and gene expression analysis to determine that these defects are remediated by SS-31 and bromoenol lactone, pharmacologic agents that bind CL or inhibit CL deacylation, respectively.
    1 context sentence
    Summary · context
    To identify unappreciated pathways of mitochondrial dysfunction in BTHS, we utilized an unbiased proteomics strategy and identified that complex I (CI) of the mitochondrial respiratory chain and the mitochondrial quality control protease presenilin-associated rhomboid-like protein (PARL) are altered in a new HEK293-based tafazzin-deficiency model.
  2. 02LabIn vitro (cells)Mechanism

    In tafazzin-deficient HEK293 cells, SS‑31 remediated the increased PARL expression.

    In plain wordsIn cells lacking tafazzin, SS‑31 corrected the raised level of the mitochondrial protease PARL.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreasePARL expression in tafazzin-deficient cells
    Study

    humann: not reported in source

    HEK293-based tafazzin-deficient cells
    Outcome group
    Mitochondrial function · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    To clarify the relationship between abnormal CL content, CI levels, and increased PARL expression that occurs when tafazzin is missing, we used blue-native PAGE and gene expression analysis to determine that these defects are remediated by SS-31 and bromoenol lactone, pharmacologic agents that bind CL or inhibit CL deacylation, respectively.
    1 context sentence
    Summary · context
    To identify unappreciated pathways of mitochondrial dysfunction in BTHS, we utilized an unbiased proteomics strategy and identified that complex I (CI) of the mitochondrial respiratory chain and the mitochondrial quality control protease presenilin-associated rhomboid-like protein (PARL) are altered in a new HEK293-based tafazzin-deficiency model.

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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