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Updated: Oct 20, 2025

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under
Francesco Napoletano1, Gloria Ferrari Bravo1, Ilaria Anna Pia Voto2
1Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy.
Abstract:
Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer's disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents TE mobilization-dependent neurodegeneration and cognitive defects. Mechanistically, PIN1 maintains nuclear type-B Lamin structure and anchoring function for heterochromatin protein 1α (HP1α). This mechanism prevents nuclear envelope alterations and heterochromatin relaxation under mechanical stress, which is a key contributor to aging-related pathologies.
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