Hugo, H. | Search bioRxiv

bioRxiv2019

ADCK4 deficiency destabilizes the coenzyme Q complex, which is rescued by 2,4-dihydroxybenzoic acid treatment

ADCK4 mutations usually manifest as steroid-resistant nephrotic syndrome, and cause coenzyme Q10 (CoQ10) deficiency. However, the function of ADCK4 remains obscure. We investigated ADCK4 function using mouse and cell models. Podocyte-specific Adck4 deletion in mice significantly reduced survival and caused severe focal segmental glomerular sclerosis with extensive interstitial fibrosis and tubular atrophy, which were prevented by treatment with 2,4-dihydroxybenzoic acid (2,4-diHB), an analog of CoQ10 precursor molecule. ADCK4 knockout podocytes exhibited significantly decreased CoQ10 level, respiratory chain activity, mitochondrial potential, and dysmorphic mitochondria with loss of cristae formation, which were rescued by 2,4-diHB treatment, thus attributing these phenotypes to decreased CoQ10 levels. ADCK4 interacted with mitochondrial proteins including COQ5, and also cytoplasmic proteins including myosin and heat shock proteins. ADCK4 knockout decreased COQ complex levels, and the COQ5 level was rescued by ADCK4 overexpression in ADCK4 knockout podocytes. Overall, ADCK4 is required for CoQ10 biosynthesis and mitochondrial function in podocytes.

genetics↗

bioRxiv2019

Peaceful behaviour: a strategy employed by an obligate nest invader to avoid conflict with its host species

In addition to its builders, termite nests are known to house a variety of secondary, opportunistic termite species, but little is known about the mechanisms governing the maintenance of such associations. In a single nest, host and intruder are likely to engage in intense conflict, due to their nestmate discrimination system. An intriguing question is how individuals cope with such a burden in the long term. Evasive behaviour has been previously suggested as a mechanism that reduces the frequency of encounters between non-nestmates. However, due to confinement imposed by the nests physical boundaries, it is likely that hosts and inquilines would eventually come across each other. Under these circumstances, it is plausible that inquilines would be required to behave accordingly to secure their housing. Here, we tested this hypothesis predicting that, once inevitably exposed to hosts, inquiline individuals would modulate their behaviour to circumvent conflict. While exploring the behavioural dynamics of the encounter between both cohabitants, we find evidence for an unusual lack of aggressiveness by inquilines towards hosts. Such a non-aggressive behaviour is characterised by evasive manoeuvres that include reversing direction, bypassing and a defensive mechanism using defecation to repel hosts. The behavioural adaptations we describe may play an intrinsic role in the stability of cohabitations between termite species: by reducing the costs of conflicts to both cohabitants, it may improve the chances for stable nest-sharing considerably.

animal behavior and cognition↗