Lysosomes and disease

Lysosomes are important in a variety of functions, including

Degradation of normal cellular proteins and other molecules (like DNA, RNA, lipids, or polysaccharides)

Disposal of abnormal proteins and other molecules

Renewal of intracellular structures (e.g. mitochondria)

Repair of plasma membrane

Release of endocytosed nutrients

Downregulation of surface receptors

Inactivation of pathogenic organisms

Antigen processing

Metal ion homeostasis

Cell death (apoptosis)

Primary as well as secondary dysfunction of lysosomes has now been recognized in a variety of diseases. Primary dysfunction is the result of a genetic defect in a protein that is directly needed in lysosomal functioning. See Molecular pathogenesis of lysosomal storage diseases.

Secondary dysfunction is increasingly recognized in a number of common diseases including Alzheimer’s disease and congestive heart failure as well as aging. Time-dependent intralysosomal accumulation of lipofuscin in non-dividing, long-lived cells is the most consistent morphologic change of aging. The mechanisms responsible for secondary lysosomal dysfunction remain poorly understood.

In case of (primary) lysosomal storage disorders, there is accumulating evidence that a defect of one specific lysosomal enzyme or function can induce subsequent defects and dysfunction within the lysosome. Consequently, the disease processes and disease progression might not be adequately predicted by assessing substrate storage and the direct impact thereof. See Disease progression