Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease.
The most striking morphologic change in neurons during normal aging is the accumulation of autophagic vacuoles filled with lipofuscin or neuromelanin pigments. These organelles are similar to those containing the ceroid pigments associated with neurologic disorders, particularly in diseases caused by lysosomal dysfunction. The pigments arise from incompletely degraded proteins and lipids principally derived from the breakdown of mitochondria or products of oxidized catecholamines. Pigmented autophagic vacuoles may eventually occupy a major portion of the neuronal cell body volume because of resistance of the pigments to lysosomal degradation and/or inadequate fusion of the vacuoles with lysosomes. Although the formation of autophagic vacuoles via macroautophagy protects the neuron from cellular stress, accumulation of pigmented autophagic vacuoles may eventually interfere with normal degradative pathways and endocytic/secretory tasks such as appropriate response to growth factors.
Sulzer
David
D
Department of Neurology, Columbia University, New York, NY 10036, USA. ds43@columbia.edu
Mosharov
Eugene
E
Talloczy
Zsolt
Z
Zucca
Fabio A
FA
Simon
John D
JD
Zecca
Luigi
L
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology; D002566:Ceroid / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014617:Vacuoles / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
D002566:Ceroid; D004396:Coloring Agents; D008062:Lipofuscin; D008543:Melanins; C014121:neuromelanin