PGAM5 helps form VDAC1 clusters that may increase ponatinib heart damage by disrupting the combined mitochondrial cleanup and stress response

Ponatinib can cause serious cardiovascular toxicity, which may be linked to mitochondrial dysfunction.

• Mitochondrial dysfunction is associated with ponatinib's cardiovascular toxicity.
• The mechanism by which ponatinib affects mitochondrial quality control is not well understood.
• The PGAM5/VDAC1 axis may play a role in ponatinib-induced cardiac injury.
• Ponatinib exposure could disrupt both mitophagy and the mitochondrial unfolded protein response.

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