Proteins are constantly exposed to environmental stressors such as free radicals and heat
shock leading to their misfolding and later to aggregation. In particular mitochondrial proteins are
challenged by reactive oxygen species (ROS) due to the oxidative metabolism of the organelle. Protein
aggregation has been associated with a wide variety of pathological conditions called proteopathies.
However, for the maintenance of protein and cellular homeostasis, mitochondria have developed
an elaborate protein quality control system consisting of chaperones and ATP-dependent proteases,
specifically employed to rescue this organelle from damage due to the accumulation of misfolded
proteins and toxic aggregates. Aging is characterized by a general decline of mitochondrial functions, correlating
with a decrease in mitochondrial protein quality control activity and an increase of free radical production. In particular in
age-related diseases like neurodegeneration, a correlation between mitochondrial damage and disease onset has been
established. In this review we summarize the current knowledge about mitochondrial protein quality control mechanisms
in mammalian cells, with a special emphasis on the role in oxidative stress and in neurodegenerative diseases.
Keywords: Alzheimer disease, mitochondrial protein quality control (mtPQC), oxidative stress, Parkinson disease.
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