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Mitochondria play a central role in energy production but also are the main cellular source of reactive oxygen species (ROS). It is widely believed that aging is related to the accumulation of oxidative molecular damage due to ROS. Aging also induces a decrease in muscle function. Recent studies indicate that caloric restriction and physical exercise suppress the decrease in muscle function though the maintaining quality of mitochondria. This review provides the current understanding of the influence of caloric restriction and exercise on mitochondrial quality control in skeletal muscle. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a genetic disorder characterized by progressive bone marrow failure, increased susceptibility to leukemia and cancer, and genomic instabilities. Protein products encoded by 22 FA genes, identified till date, cooperate in a molecular pathway called the FA pathway to repair DNA interstrand cross-links induced by chemotherapeutic agents, such as mitomycin C and cisplatin. An accumulating number of studies have shown several new functional aspects of the FA pathway, particularly in the context of the pathogenesis of bone marrow failure. This review focuses on the following topics: (1) aldehydes as intrinsic interstrand cross-linkers; (2) cytokine-induced hematopoietic stress; (3) increased transforming growth factor-β signaling; (4) mitochondrial functions of FA proteins. These findings are expected to offer new therapeutic opportunities for bone marrow failure in FA.

Congenital muscular dystrophy with mitochondrial structural abnormalities (MIM #602541), or also called megaconial congenital muscular dystrophy, is characterized clinically by early-onset muscle wasting and severe mental retardation, and pathologically by peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center on muscle biopsy. Based upon the similarity in the pathological features to rmd mouse which has a recessive mutation in Chkb gene encoding the choline kinase β that catalyzes first enzymatic step in a biosynthetic pathway for phosphatidylcholine, we have sequenced the CHKB gene in 15 patients with the disease and identified identified biallelic mutations in all patients. In muscle of three affected individuals with nonsense mutations, choline kinase activities were undetectable, and phosphatidylcholine levels were decreased while phosphatidylethanolamine levels were unchanged. Recombinant CHKB with identified missense mutations also showed reduced choline kinase activity, indicating that the disease is caused by the loss-of-function mutations in CHKB. Furthermore, mitochondria in the center of muscle fibers were subjected to autophagy on electron microscopy and these mitochondria did not have cytochrome c oxidase activity. The expression of parkin, PINK1, LC3, polyubiquitin, and p62 was upregulated in rmd muscles, indicating that mitochondria are eliminated by mitophagy.

The cellular abnormalities in Parkinson's disease (PD) are probably induced by both genetic predisposition and environmental factors. Mitochondrial dysfunction has long been implicated in the pathogenesis of PD. The recent discovery of genes associated with the etiology of familial PD has emphasized the role of mitochondrial dysfunction in PD. Recently, PINK1 and Parkin, which are associated with the mitochondria, have also enhanced the understanding of mitochondrial integrity. However, the exact mechanism underlying the functional interplay between Parkin and PINK1 remains unknown. PINK1 is rapidly and constitutively degraded under steady state conditions in a mitochondrial membrane potential dependent manner. But a loss of mitochondrial potential stabilizes PINK1 accumulation. This phenomenon may be the first step of mitochondrial elimination (mitophagy) and useful for the mitochondrial stress biomarker. Furthermore, some pathogenic mutations of PINK1 are associated with mitochondrial respiratory deficit. These results suggest that accumulation of damaged mitochondria may be the cause of early-onset familial PD.