ABSTRACT
Mitochondria surrounding lipid droplets (Peri-Droplet Mitochondria;PDM) maintain a unique proteome which is not equilibrated with the rest of the mitochondrial population. We find that PDM remain stationary and elongated on lipid droplets, fuel lipid droplet expansion, and do not fuse with cytosolic mitochondria. Compared to cytosolic mitochondria, PDM have higher capacity to metabolize pyruvate but reduced capacity to oxidize fatty acids. We reveal for the first time the mechanism by which the elongated mitochondrial shape of PDM differentiate their fuel preference from that of cytosolic mitochondria. We find that mitochondrial elongation reduces fatty acid utilization by inhibiting CPT1 activity. On the other hand, we find that mitochondrial fragmentation, such as observed in NASH, increases mitochondrial lipid utilization and may act as a compensatory mechanism to reduce lipotoxicity. Indeed, inhibition of fission in a model of NASH exacerbated NASH phenotype. We developed a cell-based imaging for the quantification of mitochondria-lipid droplet association and identified a set of small molecules that detach mitochondria from lipid droplets (PDM-Detachers). New unpublished data demonstrate PDM detachers induce lipolysis and lipid droplet shrinkage. Using these tools we assessed the role of lipid droplets in SARS-CoV2 expansion. We find that proliferation of various coronaviruses can be strongly inhibited by PDM-detachers and enhanced by attaching mitochondria to lipid droplets. We demonstrate that PDM can be found in humans. We studied adipose tissue from pheochromocytoma patients, a model of white adipose browning characterized by enhanced capacity for energy expenditure. Remarkably, bioenergetic changes associated with browning were primarily localized to PDM. Similar changes were found in a mouse model of re-browning, where PDM increased in whitened brown adipose tissue upon reducing housing temperature. Copyright © 2022
ABSTRACT
Background: Reduction in elective surgeries during the COVID-19 pandemic has negatively impacted surgical specialist training. Posterior capsule rupture rate (PCR), a complication of cataract surgery, is an objective measure of the quality of ophthalmic surgery. This study aimed to compare PCR pre- and post-COVID-19 in trainees and consultants. Methods: A single-centre consecutive case series of cataract surgeries performed at Groote Schuur Hospital, between 1 February 2017 and 31 May 2021 were analysed. Our main outcome measure was the effect of the volume of cataract surgeries on PCRs between ophthalmology trainees and consultants before and after the COVID-19 reduction in elective surgeries on 23 March 2020. Results: During the study period, 4 157 cataract surgeries were performed (3 493 in the 38 months pre-COVID-19 and 664 in the 14 months post-COVID-19). Fourteen ophthalmology trainees and six consultants performed 2 919 and 1 238 cataract surgeries, respectively. In the trainees the PCR was 4.4% pre-COVID-19 and 10.0% post COVID-19 (odds ratio [OR] 2.44;p < 0.001;CI 1.71–3.47;relative risk [RR] 2.29). The PCR of consultants remained unchanged with a PCR of 3.4% pre- and post-COVID-19 (OR 1.02;p = 0.97;CI 0.42–2.46;RR 1.02). Conclusion: COVID-19 has caused a marked reduction in the volume of cataract surgery which has resulted in a deterioration in the performance of trainees, but not consultants, and quantifies the negative impact of the pandemic on surgical training in ophthalmology. This highlights the need to develop plans to improve surgical training during the COVID-19 recovery period.