Eukaryotic lipid metabolism — In which cellular compartment of eukaryotes does the bulk of fatty acid β-oxidation (fatty acid breakdown) occur before acetyl-CoA enters the TCA cycle?

Introduction:
Understanding where fatty acids are catabolized inside eukaryotic cells is fundamental to biochemistry and physiology. This question targets the location of β-oxidation, the core pathway that converts long-chain fatty acids into acetyl-CoA for the citric acid (TCA) cycle and oxidative phosphorylation.

Given Data / Assumptions:

• Eukaryotic cells possess mitochondria and, in many tissues, peroxisomes.
• β-oxidation sequentially removes two-carbon units as acetyl-CoA.
• Carnitine shuttles long-chain fatty acyl groups into mitochondria.

Concept / Approach:
The dominant site of fatty acid β-oxidation in eukaryotes is the mitochondrial matrix. Very-long-chain fatty acids (especially > C20) undergo initial chain-shortening in peroxisomes, but full energy extraction (NADH/FADH2 feeding the electron transport chain, and acetyl-CoA oxidation in the TCA cycle) relies on mitochondria. Thus, the most accurate general answer is the mitochondrial matrix.

Step-by-Step Solution:

Verification / Alternative check:
Disorders of the carnitine shuttle or mitochondrial acyl-CoA dehydrogenases (e.g., MCAD deficiency) cause characteristic hypoketotic hypoglycemia, confirming the mitochondrial localization and physiological importance of matrix β-oxidation.

Why Other Options Are Wrong:

• Cytosol: fatty acids are activated here, but β-oxidation occurs in mitochondria, not freely in cytosol.
• Plasma membrane: not a site of oxidative catabolism.
• ER lumen: involved in lipid synthesis and desaturation, not β-oxidation.
• Peroxisome only: peroxisomes shorten very-long chains and generate H2O2; complete energy extraction requires mitochondrial β-oxidation.

Common Pitfalls:
Overgeneralizing peroxisomal involvement. Remember: peroxisomes start the job for very-long chains; mitochondria finish it and make ATP.

Final Answer:
mitochondrial matrix.