Damaged mitochondria send a protein called ubiquitin straight to the nucleus to physically rewrite genetic instructions.
April 26, 2026
Original Paper
Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling
bioRxiv · 10.64898/2026.04.24.719390
The Takeaway
Mitochondria are often called the power plants of the cell, but they also act as a sophisticated alarm system. When these power plants are damaged, they generate a phosphorylated version of the protein ubiquitin. This protein travels to the cell's command center and attaches to the DNA as an epigenetic mark. This signal tells the nucleus exactly which genes to turn on to handle the crisis. This is a direct SOS line that bypasses traditional signaling pathways to ensure the cell survives a power failure.
From the abstract
Parkinson's disease (PD) is commonly associated with dysfunctional mitochondrial homeostasis. PINK1, a S/T kinase mutated in early-onset PD, generates phosphoserine 65 ubiquitin (pS65Ub) on damaged mitochondria facilitating their removal. Here, we show that pS65Ub translocates into the nucleus after generation at damaged mitochondria and is directly attached to substrates by resident E3 ligases. Histone H2A is a major substrate and is modified at lysine 119 (H2AK119) by the polycomb silencer, E3