Heat shock protein family A (Hsp70) member 9 (HSPA9)

Heat shock protein family A (Hsp70) member 9, also known as mortalin, is a ubiquitous mitochondrial chaperone protein encoded by the HSPA9 gene in humans. Mortalin is a member of the HSP70 family and has essential roles in mitochondrial protein folding, import, and quality control, mitochondrial biogenesis, iron-sulfur cluster biogenesis, and regulation of key cellular processes including apoptosis, proliferation, and response to stress. Mortalin is expressed in multiple cellular compartments (mitochondria, cytoplasm, nucleus, ER, sometimes extracellularly). It interacts with a wide range of partners such as p53, FGF1, Dj-1, and components of the mitochondrial import machinery. Mortalin has been implicated in cancer (especially in oncogenic cell survival and resistance to apoptosis), and neurodegenerative diseases such as Alzheimer's and Parkinson's disease, where it may affect protein misfolding, oxidative stress, and mitochondrial function. Mortalin is emerging as a therapeutic target, especially in cancers with aberrant MEK-ERK signaling (like BRAF-mutant tumors), and experimental drugs such as MKT-077 and HSP70 inhibitors have been used to explore this avenue. However, due to its central homeostatic roles, therapeutic targeting poses significant safety and toxicity challenges.

Other names

MortalinGRP75Glucose-regulated protein 75Mitochondrial 70 kDa heat shock proteinPBP74mtHsp70Mot-2

Inhibition of chaperone activity (e.g., MKT-077 inhibits mortalin, leading to cell death in cancer lines) Disruption of mortalin’s stabilization of p53, mitochondrial integrity, and anti-apoptotic functions