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Autophagy delivers a biological cell's own material for digestion and recycling in lysosomes. Macroautophagy is the enclosing-carrier route illustrated here; other forms deliver cargo differently. The cargo's internal origin distinguishes this route from uptake by endocytosis.^[ref]

A lysosome is an acidic digestive and recycling organelle: one surrounding lipid bilayer encloses a lysosomal lumen containing acid hydrolases. These enzymes break down proteins, nucleic acids, carbohydrates and lipids by hydrolysis. Cargo can originate outside the biological cell, entering through endocytosis, or within its own cytoplasm, delivered through autophagy. Digestion therefore serves both disposal and reuse.^[ref]

An endosome sorts endocytosed cargo: some returns to the cell membrane, while some proceeds toward lysosomes. An autophagosome instead encloses material already in the cytoplasm. Both routes bring cargo into contact with digestive enzymes; neither implies that every internalized molecule is destroyed.^[ref]

Enzyme supply is a different itinerary from cargo disposal. Secretory protein routing and protein targeting deliver newly made digestive enzymes through the endoplasmic reticulum, Golgi apparatus and trans-Golgi network toward lysosomes.^[ref] The existing membrane transport and differential centrifugation articles explain the boundary-crossing and separation principles used below.

A proteasome is a different digestive machine: a protein complex without a surrounding lipid bilayer, acting on individual proteins in the cytosol and cell nucleus. Many targets carry ubiquitin chains. A lysosome accepts a much broader range of cargo, including material delivered inside an autophagosome. Thus an unwanted soluble protein and an unwanted mitochondrion pose different disposal problems; a proteasome does not swallow an intact mitochondrion.^[ref]

Protein degradation breaks proteins into smaller products and helps control protein abundance and quality. The ubiquitin-proteasome system selectively targets many intracellular proteins, while lysosomes degrade other material delivered by intracellular trafficking or autophagy. Synthesis and removal jointly determine abundance, so reduced protein level need not imply reduced transcription. Controlled degradation also makes some regulatory changes rapid and effectively irreversible for the individual protein molecule. ^[ref]

A ubiquitin-activating enzyme, or E1, uses ATP to activate ubiquitin and forms a covalent intermediate through a catalytic cysteine. Ubiquitin is then passed to a ubiquitin-conjugating enzyme. ATP consumption occurs at this activation stage, while the downstream relay handles targeting and transfer. This creates a chemically activated donor for controlled covalent protein modification. ^[ref]

A ubiquitin-conjugating enzyme, or E2, accepts activated ubiquitin from a ubiquitin-activating enzyme onto a catalytic cysteine. It then works with a ubiquitin ligase to transfer ubiquitin onward. Pairing between E2 and E3 helps determine which modification is assembled. This division of labour separates initial energy-dependent activation from later substrate selection and transfer. ^[ref]

A ubiquitin ligase, or E3, promotes transfer of ubiquitin to a selected substrate within the ubiquitination system. Many E3s provide substrate recognition, while the detailed chemistry differs between E3 families. A ubiquitin-conjugating enzyme supplies activated ubiquitin. The resulting modification can signal protein degradation or other fates depending on substrate, linkage and context, so ubiquitination is not synonymous with immediate destruction. ^[ref]