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Rapid rates of newly synthesized mitochondrial protein degradation are significantly affected by the generation of mitochondrial free radicals

Exposure of biological material to high levels of free radicals causes extensive cellular damage. Reactive oxygen species (ROS) generated by mitochondria have been associated with a variety of diseases and aging. We investigated the effect of low‐level mitochondrial ROS production on newly synthesized mitochondrial proteins which are potentially vulnerable to mitochondrial ROS due to their location and unfolded state. We show that elevated mitochondrial ROS increases the degradation of newly synthesized mitochondrial proteins with some proteins more sensitive than others. In the long term reduced assembly of mitochondrial complexes would affect mitochondrial function and may trigger a vicious cycle of mitochondrial ROS production.

Pharmacogenomic profiling of an oxidative stress-mediated spongiform encephalopathy

Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo

Timely elimination of damaged mitochondria is essential to protect cells from the potential harm of disordered mitochondrial metabolism and release of proapoptotic proteins. In mammalian red blood cells, the expulsion of the nucleus followed by the removal of other organelles, such as mitochondria, are necessary differentiation steps. Mitochondrial sequestration by autophagosomes, followed by delivery to the lysosomal compartment for degradation (mitophagy), is a major mechanism of mitochondrial turnover. Here we show that mice lacking the essential autophagy gene Atg7 in the hematopoietic system develop severe anemia. Atg7 −/− erythrocytes accumulate damaged mitochondria with altered membrane potential leading to cell death. We find that mitochondrial loss is initiated in the bone marrow at the Ter119 + /CD71 High stage. Proteomic analysis of erythrocyte ghosts suggests that in the absence of autophagy other cellular degradation mechanisms are induced. Importantly, neither the removal of endoplasmic reticulum nor ribosomes is affected by the lack of Atg7 . Atg7 deficiency also led to severe lymphopenia as a result of mitochondrial damage followed by apoptosis in mature T lymphocytes. Ex vivo short-lived hematopoietic cells such as monocytes and dendritic cells were not affected by the loss of Atg7. In summary, we show that the selective removal of mitochondria by autophagy, but not other organelles, during erythropoeisis is essential and that this is a necessary developmental step in erythroid cells.

Mitochondrial Reactive Oxygen Species in Mice Lacking Superoxide Dismutase 2

Critical role of complex III in the early metabolic changes following myocardial infarction

Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model

The effect of donor BMI on mitochondrial DNA copy number in isolated human pancreatic islets

Mitochondrial

The measurement of reactive oxygen species in purified heart mitochondria from the sod2 nullizygous mouse

Characterisation of undifferentiated and differentiated RD-cybrids, harbouring 3243 MELAS mutation

Dysregulated mitophagy and mitochondrial transport in severe inherited optic atrophy due to OPA1 mutations

A NOVEL CELL CULTURE MODEL FOR STUDYING HEPATIC ISCHAEMIA REPERFUSION INJURY

OPA1 plus phenotypic variation in dominantly inherited optic atrophy attributable to genetic background

Effects of stress during pregnancy on growth and adult glucose tolerance: are there implications for prenatal screening?

Mutations in the mitochondrial DNA gamma polymerase (POLG-G) may cause Alpers syndrome, mitochondrial DNA depletion and apparent non-syndromic status epilepticus: implications for valproate therapy

Molecular genetic diagnosis of mitochondrial DNA depletion syndrome and Alpers syndrome

MITOCHONDRIAL PROTECTION BY OXYGENATED PERFUSION AFTER WARM ISCHAEMIA

MITOCHONDRIAL FUNCTION DURING ISCHAEMIA-REPERFUSION IN DCD LIVERS

In utero exposure to zidovudine results in impaired glucose tolerance in mice: Implications for aids prevention in poorly nourished communities.

A study of hepatocyte ischaemia-reperfusion injury and steatosis in a human liver stem cell model