Cyclophilin D and Acetylation

Abstract

In this issue, Nguyen et al1 revealed an unexpected role of the protein posttranslational modification (PTM), lysine acetylation, in signal transduction inside cardiac mitochondria. Using a combination of proteomics and biochemical techniques, the authors discovered that the deletion of cyclophilin D (CypD−/−) results in widespread increases in the acetylation of multiple mitochondrial proteins. CypD is a mitochondrial peptidyl prolyl cis - trans isomerase best known for its role in promoting mitochondrial permeability transition (MPT) and the resulting cell death and was previously not associated with PTM signaling. The findings shed light on why CypD−/− mice had decreased fatty acid oxidation capacity in the heart and how CypD−/− loss paradoxically protects against ischemic injury but promotes heart failure. Article, see p 1308 Many recent works attempted to understand the PTM targets, occupancy, functions, and dynamics of mitochondrial proteins in the heart.2–4 These cellular signaling mechanisms are thought to fine-tune the metabolic and energetic output of the heart. Furthermore, cardioprotective PTM signals converge at cardiac mitochondria to modulate cell death outcome during ischemic injury.5 Therefore, understanding how the signals transduce inside the organelles is an outstanding objective that can lead to better therapies. It has recently emerged that lysine acetylation on nonhistone proteins is a dynamic and reversible PTM that modulates a wide range of cellular processes including metabolism.6 In a previous publication, it was found that …