What triggers a signaling cascade that leads to mitochondrial biogenesis?

• A. Sleep
• B. Repeated muscle contractions
• C. Single muscle contraction
• D. Passive stretching

Answer: (B)

Repeated muscle contractions during exercise create sustained cellular stress that activates the signaling cascade driving mitochondrial biogenesis. When muscles work hard, energy demand rises, lowering the ATP/AMP ratio and increasing calcium flux inside muscle cells. This combination turns on pathways such as AMPK and p38 MAPK, as well as calcium-activated signals like CaMK and calcineurin. These pathways converge on PGC-1α, a master coactivator that boosts the activity of transcription factors NRF1/2 and TFAM. The result is increased transcription of mitochondrial genes and replication of mitochondrial DNA, leading to more and greater mitochondria and improved oxidative capacity over time. Sleep, a single muscle contraction, or passive stretching don’t produce the same repeated, energetically demanding signals, so they’re less effective at triggering this biogenesis cascade.