- Penicillin targets bacterial cell wall synthesis by inhibiting enzymes (penicillin-binding proteins, PBPs) involved in the production of peptidoglycan. Mitochondria, although evolutionarily derived from bacteria, do not have a peptidoglycan cell wall, and therefore lack PBPs. As a result, penicillin has no direct target within mitochondria, making it non-toxic to mitochondrial function under normal conditions.
- In contrast, other antibiotics that affect bacterial ribosomes, such as tetracycline, chloramphenicol, or aminoglycosides, can sometimes impair mitochondrial protein synthesis because mitochondrial ribosomes resemble bacterial 70S ribosomes. Penicillin, however, acts on a completely different bacterial structure (the cell wall), so this cross-reactivity does not occur.
