Oxidative phosphorylation — Which chemical is classically used as an uncoupler to stop mitochondrial ATP synthesis (while allowing electron transport to continue)?

Introduction:
ATP synthesis in mitochondria depends on coupling between the electron transport chain (ETC) and ATP synthase via the proton motive force across the inner mitochondrial membrane. Certain chemicals uncouple this linkage by dissipating the gradient. This question asks you to identify a classic uncoupler used to stop ATP synthesis.

Given Data / Assumptions:

• ETC pumps protons out of the matrix, building an electrochemical gradient.
• ATP synthase uses proton return flow to phosphorylate ADP to ATP.
• Uncouplers carry protons across the membrane, collapsing the gradient.

Concept / Approach:
2,4-Dinitrophenol (DNP) is a lipid-soluble weak acid that shuttles protons across the inner mitochondrial membrane, dissipating the proton gradient. With no gradient, ATP synthase cannot operate, halting ATP production even as the ETC may run faster (increased oxygen consumption) due to loss of backpressure.

Step-by-Step Solution:

Verification / Alternative check:
Historical (and hazardous) use of DNP as a weight-loss agent increased metabolic rate and heat production, tragically confirming its uncoupling effect. Laboratory measurements show elevated O2 consumption with reduced ATP output when DNP is present.

Why Other Options Are Wrong:

• DNSA and DDT: not standard mitochondrial uncouplers in biochemistry.
• “None” is incorrect; uncouplers are well-characterized.
• Penicillin G: antibiotic targeting bacterial cell wall synthesis; unrelated to oxidative phosphorylation.

Common Pitfalls:
Confusing inhibitors (e.g., oligomycin blocks ATP synthase; rotenone/antimycin/azide block ETC complexes) with uncouplers (e.g., DNP, FCCP) that specifically collapse the gradient.

Final Answer:
2,4 dinitrophenol.