Signs of a mitochondrial stress response involving chaperones and proteases emerged as early as 1996, when Martinus et al. discovered that generating mitochondria-specific stress, by depletion of mtDNA, induces the transcriptional activation of mitochondrial chaperones’ heat shock protein 60 (HSP60) and heat shock protein 10 (HSP10) in rat hepatoma cells [11]. The gene discussed is HSPD1; the disease is hepatocellular carcinoma.