Oleaginous microorganisms (e.g. Mortierella alpina, Thraustochytrids) accumulate lipids (>20% dry wt) when the C:N ratio is high — i.e. nitrogen is exhausted but carbon (glucose) remains available. Nitrogen limitation inactivates isocitrate dehydrogenase (via AMP depletion), causing citrate accumulation in the mitochondria. Citrate is exported to the cytoplasm and cleaved by ATP-citrate lyase (ACL) to supply acetyl-CoA for de novo fatty acid synthesis.