Warburg-like effect is a hallmark of complex I assembly defects

Due to its pivotal role in NADH oxidation and ATP synthesis, mitochondrial complex I (CI) emerged as a crucial regulator of cellular metabolism. A functional CI relies on the sequential assembly of nuclear- and mtDNA-encoded subunits; however, whether CI assembly status is involved in the metabolic adaptations in CI deficiency still remains largely unknown. Here, we investigated the relationship between CI functions, its structure and the cellular metabolism in 29 patient fibroblasts representative of most CI mitochondrial diseases. Our results show that, contrary to the generally accepted view, a complex I deficiency does not necessarily lead to a glycolytic switch, i.e. the so-called Warburg effect, but that this particular metabolic adaptation is a feature of CI assembly defect. By contrast, a CI functional defect without disassembly induces a higher catabolism to sustain the oxidative metabolism. Mechanistically, we demonstrate that reactive oxygen species overproduction by CI assembly intermediates and subsequent AMPK-dependent Pyruvate Dehydrogenase inactivation are key players of this metabolic reprogramming. Thus, this study provides a two-way-model of metabolic responses to CI deficiencies that are central not only in defining therapeutic strategies for mitochondrial diseases, but also in all pathophysiological conditions involving a CI deficiency

CLUH couples mitochondrial distribution to the energetic and metabolic status

Mitochondrial dynamics and distribution are critical for supplying ATP in response to energy demand. CLUH is a protein involved in mitochondrial distribution whose dysfunction leads to mitochondrial clustering, the metabolic consequences of which remain unknown. To gain insight into the role of CLUH on mitochondrial energy production and cellular metabolism, we have generated CLUH-knockout cells using CRISPR/Cas9. Mitochondrial clustering was associated with a smaller cell size and with decreased abundance of respiratory complexes, resulting in oxidative phosphorylation (OXPHOS) defects. This energetic impairment was found to be due to the alteration of mitochondrial translation and to a metabolic shift towards glucose dependency. Metabolomic profiling by mass spectroscopy revealed an increase in the concentration of some amino acids, indicating a dysfunctional Krebs cycle, and increased palmitoylcarnitine concentration, indicating an alteration of fatty acid oxidation, and a dramatic decrease in the concentrations of phosphatidylcholine and sphingomyeline, consistent with the decreased cell size. Taken together, our study establishes a clear function for CLUH in coupling mitochondrial distribution to the control of cell energetic and metabolic status

Melissopalynological, physicochemical and antioxidant properties of honey from West Coast of Malaysia

Stingless bees are native to tropical region and produce honey which are high in moisture content. Compared to honey from honeybees, there are limited studies on honey derived from stingless bees. Hence, the aim of this study was to evaluate the chemical composition and antioxidant activities of stingless bee honey. Fifteen types of honey were collected from six states in West Coast of Malaysia and pollen analyses were carried out. Four types of unifloral honey samples produced by stingless bees were selected to determine their physicochemical and antioxidant activities including total phenolic, total flavonoid and ascorbic acid contents. Melissopalynological study of 15 honey samples collected from different states showed presence of both unifloral and multifloral origins. Honey samples collected from Apis mellifera (honeybee) combs had lower number of total pollen compared to samples collected from Heterotrigona itama and Geniotrigona thoracica (stingless bees). Jambul Merak honey contains the highest phenolic and flavonoid contents with greatest color intensity and has the highest antioxidant potential. This study highlights the chemical composition and biological activity of honey from stingless bees which may increase its commercial value or to be utilised as potential functional food ingredient

Analysis by detached leaf assay of components of partial resistance of faba bean (Vicia faba L.) to chocolate spot caused by Botrytis fabae Sard.

Five faba bean (Vicia faba L.) genotypes with different levels of field susceptibility to chocolate spot caused by Botrytis fabae, were analysed for the components of partial resistance in a laboratory assay on living detached leaves. The incubation period (IP), the number of spots (NP), the lesion diameter (LD), the latency period (LP) and the number of spores/leaflet (NS), were determined and statistically analysed. Parameters LD, LP and NS were involved in characterising partial resistance, but IP did not appear to play a role. NS did not become a significant factor until 20 h after inoculation. Genotype FRY167 was most resistant with the lowest LD and NS values and the longest LP. In contrast, FRY30 had the highest level of susceptibility, with the highest LD and NS and the shortest LP. However, the resistant control BPL710 showed a slight deviation in that it expressed a long LP which was not significantly different from the values of the susceptible control Aguadulce. The absence of a correlation between LP and NS in BPL710 opens a discussion on the genetic control of its resistance