Fission-independent compartmentalization of mitochondria during budding yeast cell division.

Lateral diffusion barriers compartmentalize membranes to generate polarity or asymmetrically partition membrane-associated macromolecules. Budding yeasts assemble such barriers in the endoplasmic reticulum (ER) and the outer nuclear envelope at the bud neck to retain aging factors in the mother cell and generate naïve and rejuvenated daughter cells. However, little is known about whether other organelles are similarly compartmentalized. Here, we show that the membranes of mitochondria are laterally compartmentalized at the bud neck and near the cell poles. The barriers in the inner mitochondrial membrane are constitutive, whereas those in the outer membrane form in response to stresses. The strength of mitochondrial diffusion barriers is regulated positively by spatial cues from the septin axis and negatively by retrograde (RTG) signaling. These data indicate that mitochondria are compartmentalized in a fission-independent manner. We propose that these diffusion barriers promote mitochondrial polarity and contribute to mitochondrial quality control.

Periodontitis and the incidence of metabolic syndrome: An 8-year longitudinal study of an adult Japanese cohort.

AIM: To examine the effect of periodontitis on the development of metabolic syndrome (MetS) and MetS components. MATERIALS AND METHODS: This study included 4761 participants aged 30-74 years who underwent health examinations at both baseline and 8-year follow-up. The Japanese MetS criteria were used for diagnosis. The Community Periodontal Index was used to assess periodontal status. The association between periodontal status and MetS incidence was examined by Poisson regression analysis. RESULTS: Multivariate analysis revealed that individuals with a ≥6 mm periodontal pocket had a significantly higher relative risk (RR) for MetS onset, as compared to individuals without deep periodontal pockets (adjusted RR 1.30, 95% confidence interval [CI]: 1.01-1.67). Compared to individuals without a deep periodontal pocket, individuals with a ≥6 mm periodontal pocket had significantly higher RRs for developing two components of MetS; the RRs were 1.25 (95% CI: 1.01-1.56) for abdominal obesity and 1.39 (95% CI: 1.03-1.86) for hyperglycaemia. CONCLUSIONS: Individuals with periodontitis had a significantly higher risk of MetS onset, possibly due to the influence of periodontitis on abdominal obesity and hyperglycaemia.

Association between oral health and locomotive syndrome: a cross-sectional study in Japanese adults.

BACKGROUND: Many studies have examined the association between oral health, care needs, and physical function, but few have focused on the association between oral health and locomotive syndrome (LS). We examined the association between LS and oral-health status, such as the number of teeth and chewing function, in an adult population. METHODS: The study included 2888 participants who underwent examinations of motor function and oral health. Individuals with LS stage 1 or higher were classified as having LS, while others were classified as not having it. Logistic regression analysis was performed using the presence or absence of LS as the dependent variable and age, sex, smoking status, drinking habit, exercise habit, walking speed, history of stroke, bone density, body mass index, metabolic syndrome, chewing function, and the number of teeth as independent variables to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for each independent variable. RESULTS: When the number of teeth and chewing function were included separately in multivariate analyses, the OR for LS was significantly higher for participants with 0-19 teeth than for those with 28 teeth, and for participants with poor chewing function than for those with good function (adjusted ORs, 1.47 [95% CI, 1.01-2.15] and 1.73 [95% CI, 1.37-2.18], respectively). In analyses that included tooth number and chewing function as a combined independent variable, relative to individuals with 28 teeth and good masticatory function, the adjusted ORs were 2.67 (95% CI, 1.57-4.52) for those with 28 teeth and poor chewing function, 1.63 (95% CI, 1.20-2.22) for those with 20-27 teeth and poor chewing function, and 1.83 (95% CI, 1.06-3.18) for those with 0-19 teeth and poor chewing function. CONCLUSION: Having fewer teeth and poor chewing function may be associated with LS. The maintenance of masticatory function may be important to prevent LS in adulthood.

Periodontitis and the incidence of chronic obstructive pulmonary disease: A longitudinal study of an adult Japanese cohort.

AIM: To examine the relationship between periodontitis as an independent effect of smoking and the development of chronic obstructive pulmonary disease (COPD) in Japanese people based on longitudinal data. MATERIALS AND METHODS: We targeted 4745 people who underwent pulmonary function tests and dental check-ups at baseline and 8 years later. The Community Periodontal Index was used to assess periodontal status. A Cox proportional hazard model was used to examine the relationship between the incidence of COPD and periodontitis and smoking. To clarify the interaction between smoking and periodontitis, interaction analysis was performed. RESULTS: In a multivariable analysis, both periodontitis and heavy smoking had significant effects on COPD development. When periodontitis was analysed as a continuous value (number of sextants with periodontitis) and as a category (presence or absence of periodontitis) in the multivariable analyses after adjusting for smoking, pulmonary function and other variables, periodontitis had significantly higher hazard ratios (HRs) for the incidence of COPD; the HRs were 1.09 (1.01-1.17) and 1.48 (1.09-2.02), respectively. Interaction analysis showed no significant interaction between heavy smoking and periodontitis on COPD. CONCLUSIONS: These results suggest that periodontitis has no interaction with smoking but has an independent effect on developing COPD.

Association of self-rated chewing function and oral health status with metabolic syndrome.

PURPOSE: The study aimed to examine the association of self-rated chewing function, the number of teeth and periodontal status with metabolic syndrome. METHODS: The participants were 11,119 adults aged 40-74 years who underwent specific health checkups, including an oral health examination, in 2018 in Japan. This study used the standard questions of the specific health checkups to obtain information on self-rated chewing function. A multinomial logistic regression analysis was performed with metabolic syndrome status as the dependent variable, and age, sex, lifestyle questions, self-rated chewing function, number of teeth, and periodontal status as the independent variables. RESULTS: Number of teeth and periodontal status were significantly associated with metabolic syndrome after adjusting for confounding variables. Self-rated chewing function was significantly associated with metabolic syndrome in the crude analysis, but not after adjustment for confounding variables. Both number of teeth and periodontal status were significantly associated with self-rated chewing function. CONCLUSION: There was no significant direct association between self-rated chewing function and metabolic syndrome. Self-rated chewing function may be an indicator of poor oral condition that links to metabolic syndrome.

Monitoring and Measuring Autophagy.

Autophagy is a cytoplasmic degradation system, which is important for starvation adaptation and cellular quality control. Recent advances in understanding autophagy highlight its importance under physiological and pathological conditions. However, methods for monitoring autophagic activity are complicated and the results are sometimes misinterpreted. Here, we review the methods used to identify autophagic structures, and to measure autophagic flux in cultured cells and animals. We will also describe the existing autophagy reporter mice that are useful for autophagy studies and drug testing. Lastly, we will consider the attempts to monitor autophagy in samples derived from humans.

Transgenic rescue of Atg5-null mice from neonatal lethality with neuron-specific expression of ATG5: Systemic analysis of adult Atg5-deficient mice.

Atg5-null mice are neonatal lethal. We have revealed in our recent paper that these mice die due to neuronal dysfunction resulting in suckling failure. Our new mouse model, atg5-/-;Eno2/Nse-Atg5 mice, where Atg5 is deficient in the whole body except for neurons, enables us to analyze the consequences of macroautophagy/autophagy-deficiency in the whole body of adult mice.

Is there an occupational status gradient in the development of periodontal disease in Japanese workers? A 5-year prospective cohort study.

BACKGROUND: Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese workers. METHODS: In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders. RESULTS: Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women. CONCLUSIONS: We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population.

Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons.

Autophagy is a cytoplasmic degradation system that is important for starvation adaptation and cellular quality control. Previously, we reported that Atg5-null mice are neonatal lethal; however, the exact cause of their death remains unknown. Here, we show that restoration of ATG5 in the brain is sufficient to rescue Atg5-null mice from neonatal lethality. This suggests that neuronal dysfunction, including suckling failure, is the primary cause of the death of Atg5-null neonates, which would further be accelerated by nutrient insufficiency due to a systemic failure in autophagy. The rescued Atg5-null mouse model, as a resource, allows us to investigate the physiological roles of autophagy in the whole body after the neonatal period. These rescued mice demonstrate previously unappreciated abnormalities such as hypogonadism and iron-deficiency anemia. These observations provide new insights into the physiological roles of the autophagy factor ATG5.

The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis.

WDR45/WIPI4, encoding a WD40 repeat-containing PtdIns(3)P binding protein, is essential for the basal autophagy pathway. Mutations in WDR45 cause the neurodegenerative disease ß-propeller protein-associated neurodegeneration (BPAN), a subtype of NBIA. We generated CNS-specific Wdr45 knockout mice, which exhibit poor motor coordination, greatly impaired learning and memory, and extensive axon swelling with numerous axon spheroids. Autophagic flux is defective and SQSTM1 (sequestosome-1)/p62 and ubiquitin-positive protein aggregates accumulate in neurons and swollen axons. Nes-Wdr45(fl/Y) mice recapitulate some hallmarks of BPAN, including cognitive impairment and defective axonal homeostasis, providing a model for revealing the disease pathogenesis of BPAN and also for investigating the possible role of autophagy in axon maintenance.

Autophagy machinery in the context of mammalian mitophagy.

Autophagy is an intracellular catabolic system that degrades cytoplasmic proteins and organelles. Damaged mitochondria can be degraded by a selective type of autophagy, which is termed mitophagy. PINK1-Parkin-dependent mitophagy has been extensively studied in the mammalian system. PINK1 accumulates on damaged mitochondria to recruit Parkin, which subsequently ubiquitinates a broad range of outer mitochondrial membrane proteins. Ubiquitinated mitochondria associate with the autophagosome formation site, and are selectively incorporated into autophagosomes. During this process, damaged mitochondria first associate with the autophagosome formation site together with upstream autophagy factors, then are efficiently incorporated into autophagosomes through binding with autophagosome adaptors. This "two-step model" may be applied to other selective types of autophagy.

Enhanced visualization of small peptides absorbed in rat small intestine by phytic-acid-aided matrix-assisted laser desorption/ionization-imaging mass spectrometry.

Enhanced visualization of small peptides absorbed through a rat intestinal membrane was achieved by matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-IMS) with the aid of phytic acid as a matrix additive. Penetrants through intestinal peptide transporter 1, i.e., glycyl-sarcosine (Gly-Sar, 147.1 m/z) and antihypertensive dipeptide, Val-Tyr (281.2 m/z), were chosen for MALDI-IMS. The signal-to-noise (S/N) ratios of dipeptides Gly-Sar and Val-Tyr were seen to increase by 2.4- and 8.0-fold, respectively, when using a 2',4',6'-trihydroxyacetophenone (THAP) matrix containing 5.0 mM phytic acid, instead of the THAP matrix alone. Owing to the phytic-acid-aided MALDI-IMS method, Gly-Sar and Val-Tyr absorbed in the rat intestinal membrane were successfully visualized. The proposed imaging method also provided useful information on intestinal peptide absorption; to some extent, Val-Tyr was rapidly hydrolyzed to Tyr by peptidases located at the intestinal microvillus during the absorption process. In conclusion, the strongly acidic additive, phytic acid, is beneficial for enhancing the visualization of small peptides using MALDI-IMS, owing to the suppression of ionization-interfering salts in the tissue.

Is there a relationship between periodontal disease and smoking after adjusting for job classification in Japanese employed males?

OBJECTIVES: The objective of this study is to examine whether the well-known association between periodontal disease and smoking persists after adjusting for job classification. METHODS: A sample of 16,110 employed Japanese males aged 20-69 years was included in the study. Periodontal examinations were conducted using the Community Periodontal Index. The association between periodontal disease and smoking status was examined using logistic regression adjusting for age, diabetes and job classification. Job classification was based on criteria of the Japanese Ministry of Health, Labour and Welfare. There are nine major job groups: (1) Professional (professionals, specialists), (2) Managers, (3) Office workers (computer operators, clerks, secretaries), (4) Skilled worker (factory workers, construction workers), (5) Salesperson (shop assistants), (6) Service occupations (superintendents, cleaners or car park attendants), (7) Security (guards), (8) Farmers and fishermen, (9) Transport and telecommunication workers (truck drivers). RESULTS: Current and former smokers were more likely to have periodontal disease than non-smokers. Adjusting for job classification attenuated the association between smoking and periodontal disease but did not eliminate the association. The odds ratios for the association between smoking and Community Periodontal Index score 3 or 4 attenuated from 2.25 to 2.04 and from 2.62 to 2.52 for individuals aged 20 to 39 and 40 to 69 years, respectively. The effect of job classification on the association between periodontal disease and smoking was higher among younger participants aged 20 to 39 years. CONCLUSIONS: Smoking persisted as an important determinant of periodontal disease after adjusting for job classification in Japanese employed males.

Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane.

Upon mitochondrial depolarization, Parkin, a Parkinson disease-related E3 ubiquitin ligase, translocates from the cytosol to mitochondria and promotes their degradation by mitophagy, a selective type of autophagy. Here, we report that in addition to mitophagy, Parkin mediates proteasome-dependent degradation of outer membrane proteins such as Tom20, Tom40, Tom70, and Omp25 of depolarized mitochondria. By contrast, degradation of the inner membrane and matrix proteins largely depends on mitophagy. Furthermore, Parkin induces rupture of the outer membrane of depolarized mitochondria, which also depends on proteasomal activity. Upon induction of mitochondrial depolarization, proteasomes are recruited to mitochondria in the perinuclear region. Neither proteasome-dependent degradation of outer membrane proteins nor outer membrane rupture is required for mitophagy. These results suggest that Parkin regulates degradation of outer and inner mitochondrial membrane proteins differently through proteasome- and mitophagy-dependent pathways.

Temporal association of elevated C-reactive protein and periodontal disease in men.

BACKGROUND: Most studies on the relationship between serum C-reactive protein (CRP) and periodontal disease have been cross-sectional. In this study, we investigated the temporal association between CRP and periodontal disease by following a large number of subjects for 1 year. METHODS: We studied 11,162 men in Nagoya, Japan, who had an initial dental examination as part of a complete physical examination and then underwent the same examination 1 year later. For the 4,997 men without periodontal disease at baseline, logistic regression analysis was performed to examine the relationship between baseline CRP and periodontal disease 1 year later, adjusting for age, body mass index, glycosylated hemoglobin A1c level, and smoking status. Similarly, logistic regression analysis was performed to examine the relationship between periodontal disease at baseline and CRP 1 year later for the 10,376 men with normal baseline CRP, adjusting for the same confounding factors. RESULTS: Among men without high CRP at baseline, periodontal disease at baseline correlated to CRP 1 year later. The odds ratio was 1.336 (95% confidence interval [CI]: 1.115 to 1.674). However, in the men without periodontal disease, no significant correlations were seen with baseline CRP or periodontal disease 1 year later. The odds ratio was 1.163 (95% CI: 0.894 to 1.513). CONCLUSION: Periodontal disease increased the risk for high serum CRP levels in men after 1 year of follow-up.

Site specific mineral composition and microstructure of human supra-gingival dental calculus.

Dental calculus has been implicated in the aetiology of several periodontal conditions. Its prevention and removal are therefore desirable clinical goals. While it is known that calculus is very variable in chemical composition, crystallinity and crystallite size little is known about site specific variability within a dentition and between individuals. With this in mind, a study was undertaken to investigate the comparative site specific nature and composition of human dental supra-gingival dental calculus obtained from 66 male patients visiting for their dental check-up using fluorescent X-ray spectroscopy, X-ray diffractometry and Fourier transform infrared spectroscopy. The supra-gingival dental calculus formed on the lingual surfaces of lower anterior teeth and the buccal surfaces of upper molar teeth were classified into four types based on calcium phosphate phases present. There was significant difference in composition of the crystal phase types between lower and upper teeth (p<0.01). There was no significant difference in crystal size between dental calculus on anterior or molar teeth of all samples. The degree of crystallinity of dental calculus formed on the upper molar teeth was higher than that formed on the lower anterior teeth (p<0.01). The CO(3)(2-) contents in dental calculus formed on the lower anterior teeth were higher than on upper molar teeth (p<0.05) which might explain the difference in crystallinity. Magnesium and Si contents and Ca:P ratio on the other hand showed no significant difference between lower and upper teeth. It was concluded that the crystal phases, crystallinity and CO(3)(2-) contents of human dental supra-gingival dental calculus is related to its location in the mouth.

Gradients in periodontal status in Japanese employed males.

AIM: The objective was to assess whether there was a social gradient in periodontal status by job classification in Japanese male workers. MATERIAL AND METHODS: Study participants were 15,803 Japanese male workers aged 20-69 years. There were seven groups classified by jobs. Oral examinations were conducted using community periodontal index (CPI). RESULTS: The percentages of sextants with a CPI score of 3 or 4 of professionals were significantly lower than for other job classes. The gradient also existed for the percentage of sextants with CPI score 4. After adjusting for age, a history of diabetes mellitus and smoking status, those lower on the gradient, namely, drivers, service occupations, salespersons and managers were 2.0, 1.5, 1.4 and 1.4, times, respectively more likely to have one or more sextants with CPI score 3 or 4 compared with professionals. Odds ratios of having more than one or more sextants with CPI score 4 after adjusting for age, clinical history of diabetes mellitus and smoking status for drivers, service occupations, salespersons and managers were 2.1, 1.5, 1.5 and 1.2, respectively, compared with professionals. CONCLUSIONS: There was a gradient in periodontal status by job classification. Professional and office workers had better periodontal status than salespersons, service occupations and drivers.

Is there a gradient by job classification in dental status in Japanese men?

The objective of this study was to assess whether there is a gradient in dental health status by job classification in male Japanese workers. The study subjects were 16,261 male Japanese workers aged 20-69 yr. Jobs were classified into seven job groups. Oral examination was conducted using World Health Organization criteria for decayed, missing or filled teeth (DMFT). Professionals, managers, and office workers had a better oral status than those in service occupations and drivers. Professionals had significantly more natural and sound teeth than those in other job classes. The DMFT of professionals was significantly lower than in workers of other job classes. Professionals had a significantly higher restorative index than did workers of other job classes. The restorative index of office workers was significantly higher than that in managers, skilled workers, salespersons, those in service occupations, and drivers. Drivers were 1.8 times, and those in service occupations 1.3 times, more likely to have one or more carious teeth compared with professionals. Skilled workers, salespersons, those in service occupations, and drivers were 1.3, 1.3, 1.4, and 2.1 times, respectively, more likely to have a missing tooth compared with professionals. Skilled workers, those in service occupations, and drivers were 1.7, 1.9, and 3.1 times, respectively, more likely not to have 20 or more teeth compared with professionals aged 50-69 yr.