60 kDa heat shock protein, mitochondrial (HSP60)

The 60 kDa heat shock protein, mitochondrial (HSP60), also known as HSPD1, is a highly conserved molecular chaperone primarily located in the mitochondrial matrix [1, 10]. It functions as a chaperonin, working in tandem with the co-chaperonin HSP10 to facilitate the ATP-dependent folding and assembly of proteins imported into the mitochondria, thereby maintaining organelle proteostasis [10, 14]. Beyond its canonical mitochondrial role, HSP60 is found in the cytosol and extracellular space, where it can act as a pro-inflammatory 'danger signal' or modulate apoptotic pathways depending on the cellular context [1, 11]. In many cancers, HSP60 is overexpressed and promotes tumor cell survival by inhibiting pro-apoptotic signaling and stabilizing pro-survival proteins like survivin [5, 18]. Conversely, mutations in the HSPD1 gene are associated with neurodegenerative disorders such as spastic paraplegia 13 and hypomyelinating leukodystrophy [7, 18]. Therapeutic strategies targeting HSP60 involve small-molecule inhibitors, such as KHS101 and suramin, which disrupt its ATPase activity or chaperonin cycle [1, 15]. However, the essential nature of HSP60 in normal mitochondrial function across all tissues presents a significant challenge for drug development, as systemic inhibition may lead to substantial toxicity [1, 15].

Other names

HSPD1Chaperonin 60CPN60Heat shock protein 60HSP-60HuCHA60Mitochondrial matrix protein P1P60 lymphocyte proteinGROELSPG13HLD4

Inhibition of ATPase activity and disruption of the chaperonin-mediated protein folding cycle [1, 13, 15].